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Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36—a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs—a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) which is associated with inflammation, thrombosis edema, hemorrhage, intra-alveolar fibrin deposition, and vascular and pulmonary damage. In COVID-19, the coronavirus activates macrophages by inducing the generation of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18 and TNF] that can damage endothelial cells, activate platelets and neutrophils to produce thromboxane A2 (TxA2), and mediate thrombus generation. In severe cases, all these phenomena can lead to patient death. The binding of SARS-CoV-2 to the Toll Like Receptor (TLR) results in the release of pro-IL-1β that is cleaved by caspase-1, followed by the production of active mature IL-1β which is the most important cytokine in causing fever and inflammation. Its activation in COVID-19 can cause a "cytokine storm" with serious biological and clinical consequences. Blockade of IL-1 with inhibitory and anti-inflammatory cytokines represents a new therapeutic strategy also for COVID-19. Recently, very rare allergic reactions to vaccines have been reported, with phenomena of pulmonary thrombosis. These side effects have raised substantial concern in the population. Highly allergic subjects should therefore be vaccinated under strict medical supervision. COVID-19 has accelerated vaccine therapy but also the use of drugs and monoclonal antibodies (mABs) which have been used in COVID-19 therapy. They are primarily adopted to treat high-risk mild-to-moderate non-hospitalized patients, and it has been noted that the administration of two mABs gave better results. mABs, other than polyclonal plasma antibodies from infected subjects with SARS-CoV-2, are produced in the laboratory and are intended to fight SARS-CoV-2. They bind specifically to the antigenic determinant of the spike protein, inhibiting the pathogenicity of the virus. The most suitable individuals for mAB therapy are people at particular risk, such as the elderly and those with serious chronic diseases including diabetics, hypertension and obesity, including subjects suffering from cardiovascular diseases. These antibodies have a well-predetermined target, they bind mainly to the protein S (formed by the S1A, B, C and D subtypes), located on the viral surface, and to the S2 protein that acts as a fuser between the virus and the cell membrane. Since mABs are derived from a single splenic immune cell, they are identical and form a cell clone which can neutralize SARS-CoV-2 by binding to the epitope of the virus. However, this COVID-19 therapy may cause several side effects such as mild pain, bleeding, bruising of the skin, soreness, swelling, thrombotic-type episodes, arterial hypertension, changes in heart activity, slowed bone marrow activity, impaired renal function, diarrhea, fatigue, nausea, vomiting, allergic reaction, fever, and possible subsequent infection may occur at the site of injection. In conclusion, the studies promoting mAB therapy in COVID-19 are very promising but the results are not yet definitive and more investigations are needed to certify both their good neutralizing effects of SARS-CoV-2, and to eliminate, or at least mitigate, the harmful side effects.

Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature and reside in vascularized tissues. They can be activated by antigen provoking overexpression of pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. IL-38 specifically binds only to IL-36R and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs, a process that activates macrophages to secrete pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus that infects humans and a number of animal species causing coronavirus disease-19 (COVID-19), a respiratory distress syndrome which has provoked a global pandemic and a serious health crisis in most countries across our planet. COVID-19 inflammation is mediated by IL-1, a disease that can cause symptoms such as fever, cough, lung inflammation, thrombosis, stroke, renal failure and headache, to name a few. Strategies that inhibit IL-1 are certainly helpful in COVID-19 and can represent one of the therapeutic options. However, until now, COVID-19 therapy has been scarce and, in many cases, ineffective, since there are no specific drugs other than the vaccine that can solve this serious health problem. Messenger RNA (mRNA) vaccines which are the newest approach, are already available and will certainly meet the many expectations that the population is waiting for. mRNA vaccines, coated with protected soft fatty lipids, use genetic mRNA (plus various inactive excipients) to make a piece of the coronavirus spike protein, which will instruct the immune system to produce specific antibodies. The soft fatty lipids allow the entry of mRNA into cells where it is absorbed into the cytoplasm and initiates the synthesis of the spike protein. In addition, vaccination also activates T cells that help the immune system respond to further exposure to the coronavirus. mRNA induces the synthesis of antigens of SARS-CoV-2 virus which stimulate the antibody response of the vaccinated person with the production of neutralizing antibodies. The new variant of the coronavirus-19 has been detected in the UK where, at the moment, the London government has imposed a lockdown with restrictions on international movements. The virus variant had already infected 1/4 of the total cases and in December 2020, it reached 2/3 of those infected in the UK. It has been noted that the spreading rate of the British variant could be greater than 70% of cases compared to the normal SARS-CoV-2 virus, with an R index growth of 0.4. Recent studies suggest that coronavirus-19 variation occurs at the level N501Y of the spike protein and involves 23 separate mutations on the spike, 17 of which are linked to the virus proteins, thus giving specific characteristics to the virus. In general, coronaviruses undergo many mutations that are often not decisive for their biological behavior and does not significantly alter the structure and the components of the virus. This phenomenon also occurs in SARS-CoV-2. It is highly probable that the variants recently described in the UK will not hinder vaccine-induced immunity. In fact, the variant will not break the vaccine although it may have some chance of making it a little less effective. Therefore, it is pertinent to think that the vaccine will work against the SARS-CoV-2 variant as well. In today's pandemic, the D614G mutation of the amino acid of corronavirus-19, which emerged in Europe in February 2020 is the most frequent form and causes high viral growth. The previously infrequent D614G mutation is now globally dominant. This variant, which is being tested by many international laboratories, is rapidly spreading across the countries and a series of vaccinated subjects are testing to see if their antibodies can neutralize the new variant of SARS-CoV-2. This variant has a very high viral growth and is less detectable with the RT-PCR technique in the laboratory. It has been reported that the British variant that increases viral load does not cause more severe effects in the respiratory tract and lung disease, therefore, it is certain that the variant is growing rapidly and must be kept under control; for this reason, laboratory data is expected impatiently. The study on the many variants that coronavirus-19 presents is very interesting and complete and clearer data on this topic will be ready in the near future. In addition, it is still unclear whether the different variants discovered in many countries, including Africa, share the same spike protein mutation and therefore, this is another study to elaborate on. In order to be certain and to not have unexpected surprises, we need to reduce the spread and the transmission speed of viral variants that could appear around the world, creating new pandemics. For this reason, the scientific community is on the alert since laboratory tests on serum antibodies from COVID-19 survivors have been reported to be less effective in attacking the variant. In light of the above, the scientific community must be on the alert as larger variants of the spike protein could escape vaccine-induced antibodies, which for now are of great help to the community and can save millions of lives. Deepening the study of spike protein mutations will help to better understand how to combat coronavirus-19 and its variants.

SARS-Cov-2 infection causes local and systemic inflammation mediated by pro-inflammatory cytokines and COX-2 eicosanoid products with metabolic dysfunction and tissue damage that can lead to patient death. These effects are primarily induced by IL-1 cytokines, which are involved in the elevation of hepatic acute phase proteins and fever. IL-1 has a broad spectrum of biological activities and participates in both innate and acquired immunity. In infections, IL-1 induces gene expression and synthesis of several cytokines/chemokines in both macrophages and mast cells (MCs). The activation of MCs triggers the secretion of mediators stored in the granules, and the de novo synthesis of pro-inflammatory cytokines. In microorganism infections, the release of IL-1 macrophage acts on adhesion molecules and endothelial cells leading to hypotension and septic shock syndrome. IL-1 activated by SARS-CoV-2 stimulates the secretion of TNF, IL-6 and other cytokines, a pro-inflammatory complex that can lead to cytokine storm and be deleterious in both lung and systemically. In SARS-CoV-2 septic shock, severe metabolic cellular abnormalities occur which can lead to death. Here, we report that SARS-CoV-2 induces IL-1 in macrophages and MCs causing the induction of gene expression and activation of other pro-inflammatory cytokines. Since IL-1 is toxic, its production from ubiquitous MCs and macrophages activated by SARS-CoV-2 can also provokes both gastrointestinal and brain disorders. Furthermore, in these immune cells, IL-1 also elevates nitric oxide, and the release of inflammatory arachidonic acid products such as prostaglndins and thromboxane A2. All together these effects can generate cytokine storm and be the primary cause of severe inflammation with respiratory distress and death. Although, IL-1 administered in low doses may be protective; when it is produced in high doses in infectious diseases can be detrimental, therefore, IL-1 blockade has been studied in many human diseases including sepsis, resulting that blocking it is absolutely necessary. This definitely nurtures hope for a new effective therapeutic treatment. Recently, two interesting anti-IL-1 cytokines have been widely described: IL-37 and IL-1Ra. IL-37, by blocking IL-1, has been observed to have anti-inflammatory action in rodents in vivo and in transfected cells. It has been reported that IL-37 is a very powerful protein which inhibits inflammation and its inhibition can be a valid therapeutic strategy. IL-37 is a natural suppressor of inflammation that is generated through a caspase-1 that cleaves pro-IL-37 into mature IL-37 which translocates to the nucleus and inhibits the transcription of pro-inflammatory genes; while IL-1Ra inhibits inflammation by binding IL-1 to its IL-1R (receptor). We firmly believe that blocking IL-1 with an anti-inflammatory cytokine such as IL-37 and/or IL-1Ra is an effective valid therapy in a wide spectrum of inflammatory disorders including SARS-CoV-2-induced COVID-19. Here, we propose for the first time that IL-37, by blocking IL-1, may have an important role in the therapy of COVID-19.

A novel human coronavirus SARS-CoV-2 (also referred to as CoV-19) that emerged in late 2019 causes Covid-19 disease a respiratory tract infection which provokes about 4 million deaths per year. Unfortunately, to date, there is no specific antiviral treatment for COVID-19. Mast cells (MCs) are immune cells implicated in the pathogenesis of viral infections, where they mediate inflammation. Microbes, including virus, activate MCs through TLR releasing chemical pro-inflammatory compounds and cytokines. Although, in biomedical literature there are only few reports on MCs activation by SARS-CoV-2 infection. The production of pro-inflammatory cytokines by MC viral activation leads to increase pulmonary inflammation and fibrosis. Sodium Chromo-Glycate (SCG) described as a MC stabilizer, prevents the release of inflammatory chemical compounds, improve mouse survival and respiratory pathological changes in lung viral infection and suppresses inflammation. Furthermore, palmitoylethanolamide (PEA) a nuclear factor agonist, an endogenous fatty acid amide, which exerts a variety of biological effects, related to chronic inflammation and pain, is involved also in MCs homeostasis with an inhibitory and protective effect on the respiratory tract during viral infections. Here, we hypothesize for the first time, that SCG and/or PEA suppress MC activation and pro-inflammatory mediators release, playing an anti-inflammatory therapeutic role in the inflamed lung of patients with COVID-19.

IL-1 induces a significant number of metabolic and hematological changes. In experimental animals, IL-1 treatments cause hypotension due to rapid reduction of systemic blood pressure, reduced vascular resistance, increased heart rate and leukocyte aggregations. IL-1 causes endothelial dysfunction, the triggering factor of which may be of a different nature including pathogen infection. This dysfunction, which includes macrophage intervention and increased protein permeability, can be mediated by several factors including cytokines and arachidonic acid products. These effects are caused by the induction of IL-1 in various pathologies, including those caused by pathogenic viral infections, including SARS-CoV-2 which provokes COVID-19. Activation of macrophages by coronavirus-19 leads to the release of pro-inflammatory cytokines, metalloproteinases and other proteolytic enzymes that can cause thrombi formation and severe respiratory dysfunction. Patients with COVID-19, seriously ill and hospitalized in intensive care, present systemic inflammation, intravascular coagulopathy with high risk of thrombotic complications, and venous thromboembolism, effects mostly mediated by IL-1. In these patients the lungs are the most critical target organ as it can present an increase in the degradation products of fibrin, fibrinogen and D-dimer, with organ lesions and respiratory failure. It is well known that IL-1 induces itself and another very important pro-inflammatory cytokine, TNF, which also participates in hemodynamic states, including shock syndrome in COVID-19. Both IL-1 and TNF cause pulmonary edema, thrombosis and bleeding. In addition to hypotension and resistance of systemic blood pressure, IL-1 causes leukopenia and thrombocytopenia. The formation of thrombi is the main complication of the circulatory system and functionality of the organ, and represents an important cause of morbidity and mortality. IL-1 causes platelet vascular thrombogenicity also on non-endothelial cells by stimulating the formation of thromboxane A2 which is released into the inflamed environment. IL-1 is the most important immune molecule in inducing fever, since it is involved in the metabolism of arachidonic acid which increases from vascular endothelial organs of the hypothalamus. The pathogenesis of thrombosis, vascular inflammation and angigenesis involves the mediation of the activation of the prostanoid thromboxane A2 receptor. In 1986, in an interesting article (

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.

Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4+ T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.

SARS-CoV-2, also referred to as CoV-19, is an RNA virus which can cause severe acute respiratory diseases (COVID-19), with serious infection of the lower respiratory tract followed by bronchitis, pneumonia and fibrosis. The severity of the disease depends on the efficiency of the immune system which, if it is weak, cannot stem the infection and its symptoms. The new CoV-19 spreads in the population at a rate of 0.8-3% more than normal flu and mostly affects men, since immune genes are more expressed on the X chromosome. If CoV-19 would spread with a higher incidence rate (over 10%), and affect the people who live in closed communities such as islands, it would cause many more deaths. Moreover, people from the poorest classes are most at risk because of lack of health care and should be given more assistance by the competent authorities. To avoid the aggravation of CoV-19 infection, and the collapse of the health system, individuals should remain at home in quarantine for a period of approximately one month in order to limit viral transmission. In the case of a pandemic, the severe shortage of respirators and protective clothing, due to the enormous demand and insufficient production, could lead the CoV-19 to kill a large number of individuals. At present, there is no drug capable of treating CoV-19 flu, the only therapeutic remedies are those aimed at the side effects caused by the virus, such as inflammation and pulmonary fibrosis, recognized as the first causes of death. One of the COVID-19 treatments involves inhaling a mixture of gaseous hydrogen and oxygen, obtaining better results than with oxygen alone. It was also noted that individuals vaccinated for viral and/or bacterial infectious diseases were less likely to become infected. In addition, germicidal UV radiation "breaks down" the oxygen O2 which then aggregate into O3 (ozone) molecules creating the ozone layer, capable of inhibiting viral replication and improving lung respiration. All these precautions should be taken into consideration to lower the risk of infection by CoV-19. New anti-viral therapies with new drugs should also be taken into consideration. For example, microbes are known to bind TLR, inducing IL-1, a pleiotropic cytokine, highly inflammatory, mediator of fever and fibrosis. Therefore, drugs that suppress IL-1 or IL-1R, also used for the treatment of rheumatoid arthritis are to be taken into consideration to treat COVID-19. We strongly believe that all these devices described above can lead to greater survival and. therefore, reduction in mortality in patients infected with CoV-19.

Coronavirus can cause respiratory syndrome which to date has affected about twelve thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical copounds including histamine and protease; while late activation provoke the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus maybe inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.

Chimeric antigen receptor (CAR) T cells are genetically modified T cells that act against cancer. When CAR-T cells are administered they can trigger inflammatory cytokines and increase toxicity. Interleukin (IL)-1 is the classic cytokine that mediates inflammatory reactions including those that occur in CAR-T-cell therapy. IL-1 also induces IL-33 in mast cells (MCs), amplifying the allergic reaction. IL- 37 (ILF7) is an IL-1 family member which binds IL-18 receptor alpha (IL-18Rα) chain and suppresses innate and acquired immunity. IL-37 is an anti-inflammatory cytokine which inhibits pro-inflammatory cytokines including IL-1 and IL-33. Here, we hypothesize that inflammation and toxicity generated in tumor CAR-T therapy could be inhibited by IL-37, contributing to an improvement in the treatment of tumors with CAR-T therapy.

It is now well-known that interleukins (ILs) play a pivotal role in shaping innate immunity: inflammatory ILs are responsible for all innate aspects of immune response, from the very first vascular reactions to the chronic non-specific response to inflammation; while anti-inflammatory ILs are responsible for keeping adaptive immunity at bay. The interactions between ILs and adaptive immunity have been long considered secondary to the effects on the innate immune system, but in recent years it has appeared more clearly that IL direct interactions with adaptive immunity are extremely important both in physiologic and pathologic immune response. In the present review we analyze the role of inflammatory ILs (IL-1, IL-6, IL-33 and IL-37) on adaptive immunity and briefly discuss the possible therapeutic perspectives of IL-blockade in adaptive immunity disorders.

Systemic lupus erythematosus (SLE), is a complex chronic inflammatory autoimmune disease, with rheumatological manifestations, which afflicts mainly women. SLE presents various heterogeneous clinical aspects and different pathogeneses and involves the production of anti- DNA autoantibodies which are deposited as immune complexes in various organs and tissues, provoking inflammation. These diseases cause multiple tissue and organ damage in arthritis, skin lesions, hematologic changes, renal and neurologic disorders, and others (Table I). In SLE, serum contains anti-nucleus antibodies and anti-DNA antibodies that can be important biomarkers for patients suffering from this disease.

Activated mast cells (MCs) secrete a number of compounds including pro-inflammatory and anti-inflammatory cytokines. MCs are a potential source of cytokines and chemokines which participate in allergic reactions and inflammation. MCs can be activated by IgE through its receptor FceRI, but also by Toll-like receptors and/or interleukin (IL)-1. MCs can be a target for both pro-inflammatory and anti-inflammatory cytokines. IL-1 activates MCs to release inflammatory chemical mediators, and cytokines/chemokines, an effect which can be potentially inhibited by IL-37. In addition, IL-36 is also a powerful cytokine with a pro-inflammatory activity. IL-38 binds IL-36R and inhibits the pro-inflammatory activity of IL-36, thus performing a therapeutic action. In this article we review the role of MCs in relation to pro-inflammatory and anti-inflammatory IL-1 family member cytokines and a possible therapeutic effect in inflammatory disorders.

Mast cells (MCs) are hematopoietic immune cells commonly found in adjacent to blood vessels in the lamina propria of airway mucosa. They are important in allergic reactions since the cross-linking of their surface high affinity receptor FceRI induces activation of these cells, and provokes the synthesis, degranulation and release of inflammatory mediators including arachidonic acid-derived eicosanoids (de novo synthesized), stored enzyme mediators, and inflammatory TH1 and TH2 cytokines, and chemokines. Interleukin (IL)-33 participates in innate and adaptive immunity and inflammation and, acting on CD34+ cells, causes MC differentiation and maturation. IL-33 is generated by activated immune cells, and activates MCs which degranulate and release pro-inflammatory mediators. IL-33 is very important in mediating allergic inflammation and can be induced by IL-1 beta. It is also called "alarmin" and is an inflammatory cytokine IL-1 family member, expressed from mocytes and MCs, which binds its receptor ST2, provoking its release after cell damage. MC-derived allergic compounds in response to IL-33 is critical to innate type 2 immunity. IL-37 is expressed by immune and non-immune cells after pro-inflammatory stimulus. IL-37, an anti-inflammatory cytokine, binds IL-18Ra and suppresses pro-inflammatory IL-1 beta released by activated immune cells such as macrophages. Here, we hypothesize that pro-inflammatory IL-1 family member cytokines released by activated MCs, mediating inflammatory allergic phenomenon, can be suppressed by IL-37.

The activation of brain nociceptors and neurons may lead to neurogenic inflammation, an event that involves immune cells including mast cells (MCs). Microglia are similar to macrophages and secrete pro-inflammatory IL-1 family members and TNF. TNF is rapidly released (first 10 minutes from MC granules) and is subsequently secreted along with other pro-inflammatory cytokines with a new synthesis after several hours. MC-derived TNF is a very powerful pro-inflammatory cytokine which mediates sensitization of the meningeal nociceptors. Here, we report the involvement of MCs in neuroinflammation, the role of inflammatory cytokine IL-1 family members, and of TNF, as well as the potential inhibition of IL-37.

Background Fibrosis involves the activation of inflammatory cells, leading to a decrease in physiological function of the affected organ or tissue. Aims To update and synthesize relevant information concerning fibrosis into a new hypothesis to explain the pathogenesis of fibrosis and propose potential novel therapeutic approaches. Materials and methods Literature was reviewed and relevant information is discussed in the context of the pathogenesis of fibrosis. Results A number of cytokines and their mRNA are involved in the circulatory system and in organs of patients with fibrotic tissues. The profibrotic cytokines are generated by several activated immune cells, including fibroblasts and mast cells (MCs), which are important for tissue inflammatory responses to different types of injury. MC-derived TNF, IL-1, and IL-33 contribute crucially to the initiation of a cascade of the host defence mechanism(s), leading to the fibrosis process. Inhibition of TNF and inflammatory cytokines may slow the progression of fibrosis and improve the pathological status of the affected subject. IL-37 is generated by various types of immune cells and is an IL-1 family member protein. IL-37 is not a receptor antagonist; it binds IL-18 receptor alpha (IL-18Rα) and delivers the inhibitory signal by using TIR8. It has been shown that IL-37 can be protective in inflammation and injury, and inhibits both innate and adaptive immunity. Discussion IL-37 may be useful for suppression of inflammatory diseases induced by inhibiting MyD88-dependent TLR signalling. In addition, IL-37 downregulates NF-κB induced by TLR2 or TLR4 through a mechanism dependent on IL-18Rα. Conclusion This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL-37-targeting cytokines.

Innate immunity consists of physical and chemical barriers which provide the early defense against infections. Innate immunity orchestrates the defense of the host with cellular and biochemical proteins. Mast cells (MCs) are involved in innate and adaptive immunity and are the first line of defense which generates multiple inflammatory cytokines/chemokines in response to numerous antigens. MC-activated antigen receptor Fc-RI provokes a number of important biochemical pathways with secretion of numerous vasoactive, chemoattractant and inflammatory compounds which participate in allergic and inflammatory diseases. MCs can also be activated by Th1 cytokines and generate pre-formed and de novo inflammatory mediators, including TNF. IL-37 is an anti-inflammatory cytokine which binds IL-18R-alpha chain and reduces the production of inflammatory IL-1 family members. IL-37 down-regulates innate immunity by inhibiting macrophage response and its accumulation and reduces the cytokines that mediate inflammatory diseases. Here, we discuss the relationship between MCs, innate immunity, and pro-inflammatory and anti-inflammatory cytokines.

Adaptive immune response plays an important role against bacteria and parasites, a reaction that also involves mast cell (MC) activation which participates in innate and adaptive immunity. In allergic reactions there is a TH2 immune response with generation of allergen-specific IgE antibodies. In MCs, IgE cross-link FcRI high affinity receptor and activate tyrosine kinase proteins, leading to stimulation of NF-κB and AP-1 resulting in the release of a number of cytokines/chemokines and other compounds. Through their proteolytic pathways, MCs may process the antigen for presentation to CD4+ cells which release TH2 cytokines and growth factors, which play an important role in asthma, allergy, anaphylaxis and inflammation. Thus, MCs can contribute to adaptive immunity. MCs may also be activated though the TLR-dependent pathway which is controlled by several proteins including myeloid differentiation factor 88 (MyD88) which can be inhibited by interleukin (IL)-37. Here, we describe the participation of MCs in adaptive immunity and inflammation, an effect that may be inhibited by IL-37.

IL-1 family members include inflammatory and anti-inflammatory cytokines. They can be beneficial or detrimental, not only in cancer, but also in inflammatory conditions. Mast cells (MCs) originate from CD34+/CD117+/CD13+ pluripotent hematopoietic stem cells, express c-Kit receptor (c-Kit-R), which regulates the proliferation and sustain the survival, differentiation and maturation of MCs. They are immune cells involved in innate and adaptive immunity, allergy, autoimmunity, cancer and inflammation. MCs along with T cells and macrophages release interleukin (IL)-10, which is a pleiotropic immunoregulatory cytokine with multiple biological effects. IL-10 inhibits Th1 inflammatory cells, in particular TNF mostly generated by macrophages and MCs, and down-regulates IFN-γ, IL-1 and IL-6. IL-37 is a family member cytokine which binds IL-18 receptor α chain and inhibits inflammatory mediators including TNF, IL-1, IL-6, IL-33 and nitric oxide (NO). IL-37 similar to IL-10 inhibits MC inflammatory cytokines in several disorders, including asthma, allergy, arthrtitis and cancer. Here we report a study comparing IL-10 with IL-37, two anti-inflammatory cytokines.

The major aim of this study is to provide a review of the research studies regarding the clinical link between alexithymia and interleukins (IL). We performed a search for the relevant literature by using search terms as "alexithymia" combined with "interleukin or IL". A total of 9 original research studies were identified and included. Alexithymia was found to be prevalent in inflammatory response and associated with inflammatory cytokines. Our review emphasized for the first time the relationships of alexithymia with inflammatory response mediated by IL-1 family members. Therefore, the screening of alexithymic traits and the administration of appropriate psychological and psychotherapeutical interventions should be integral parts of disease management programs. Supplying such interventions will probably help with prevention of the development of the disease and/or its exacerbation by improving the quality of life of alexithymic individuals.

Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic protein-1 (MCP-1), RANTES and stem cell factor (SCF) to selectively secrete inflammatory molecules including chemical mediators and cytokines (TNF, IL-6 and IL-1). However, MC differentiation pathways and heterogeneity in cancer are still poorly understood. Human interleukin 1 (IL-1) plays a pivotal role in the pathogenesis of many diseases and functions, including host response to microbial invasion, injury inflammatory processes, immunologic challenges and cancer. Inflammation around the tumor includes the infiltration of mast cells and facilitates cancer growth. MCs are activated by IL-1 which can be produced by certain cancer cells and stimulate the stromal cells to selectively release IL-6, contributing to the development of Th-17 cells and increasing inflammation. IL-37, mainly generated by macrophage cell line, is an IL-1 family member which binds IL-18 receptor α (IL-18Rα) chain, and acts as a natural inhibitor of immune responses. IL-37 down-regulates cJun induced by IL-1, pro-inflammatory signals and reduces the expression of the mitogen-activated protein kinase (MAPK) p38α, STAT transcription factors and p53, affecting cellular differentiation and proliferation. In the present study we report the relationship between inflammatory mast cells, cancer and the beneficial effect of IL-37.

Cancer includes a number of related diseases due to abnormal cell proliferation that spreads to nearby tissues. Many compounds (physical, chemical and biological) have been used to try to halt this abnormal proliferation, but the therapeutic results are poor, due also to the side effects. It has been reported that ecto-nicotinamide adenine dinucleotide oxidase di-sulfide-thiol exchanger 2 (ENOX2), also known as tumor-associated nicotinamide adenine dinucleotide oxidase (tNOX), was found to be located on the cancer cell surface, essential for cancer cell growth. Capsaicin and other anti-oxidants are capable of inhibiting tNOX, causing apoptosis of cells, exerting anti-tumor activity. It is interesting that some authors reported that ENOX2 is present in the serum of cancer patients several years before the clinical symptoms of the tumor. However, this result has to be confirmed. In this article we discuss ENOX2 and its inhibition as a hope of improving cancer therapy.

Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, β2--adrenoreceptor (β2AR) pathway, cortisol, epinephrine and norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and skin diseases. Substance P is a neuropeptide released in the skin from the peripheral nerve and is related to stress and inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of cytokines/chemokines. Corticotropin-releasing hormone (CRH), produced by mast cells, is a neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including cAMP, protein kinase C, and mitogen-activated protein kinases (MAPK). Under stress, CRH, glucocorticoids, epinephrine and cytokines are generated. Moreover, the release of ACTH binds the receptor MC2-R and stimulates the generation of glucocorticoids such as corticosterone and cortisol, which interact with the transcription factors AP-1 and NF-kB. In skin keratinocytes, ACTH promotes the generation of pro-inflammatory cytokines, which enhances T-cell activity. Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and cytokine/chemokine production. However, glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand, cytokines, such as TNF, IL-1 and IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory cytokines and neurogenic inflammatory pathways.

Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.

Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.

Στη μeλέτη αυτή παρουσιάζονται για πρώτη φορά στην Eλλάδα πeριστατικά ουρολοίμωξης σe σύeς μιας βιομηχανικού τύπου eκτροφής χοίρων. Σe διάστημα eνός έτους καταγράφηκαν 21 πeριστατικά ουρολοιμώξeων που eμφανίζονταν μeταξύ της 2ης και 5ης eβδομάδας μeτά την οχeία και διαρκούσαν 2 έως 7 ημέρeς. Τα πeριστατικά αυτά αντιστοιχούσαν στο 5,8% των τοκeτών που πραγματοποιήθηκαν στην eκτροφή. Χαρακτηρίζονταν από ανορeξία, πολυδιψία και αιματουρία, μe απόληξη συνήθως το θάνατο, eνώ οι σύeς που eπιβίωναν eμφάνιζαν προοδeυτική απώλeια του σωματικού τους βάρους. Παρατηρήθηκe δe σημαντική συσχέτιση του αριθμού των συών που πέθαναν τόσο μe τον αριθμό των συών που eμφάνισαν ανορeξία (ρ

The beneficial effect of dietary inclusion of natural zeolites on the growth of the animals and on reducing ammonia levels in livestock buildings, has been escribed. The objective of the present study was to determine the effect of the dietary inclusion of a natural zeolite (clinoptilolite) on the ammonia level in a Greek "farrow-to-finish" pig unit. Animals participating in the study were of the same genetic background and were divided into two main experimental groups depending on the inclusion or not of clinoptilolite (groups Ζ and Νrespectively) and four experimental subgroups depending on the inclusion or not of antimicrobials in the feed (subgroups Zl9 Nx and Z2, N2 respectively). Aerial ammonia level measurements were carried out using diffusion tubes (Dräger tubes) at the end of each growth stage (weaning, growing and fattening stages). In order to ensure the accuracy of the measurements, in each barn, animals of the same experimental subgroup were allocated. The results of this study demonstrate that the incorporation of clinoptilolite in swine feed had a favorable effect on aerial ammonia level. Significantly lower levels (P

Ο κλeιστοί θάλαμοι των βιομηχανικού τύπου eκτροφών χρησιμοποιούνται πλέον σe ολόκληρο τον κόσμο για την eκτροφή χοίρων. Παρά τα οικονομικά πλeονeκτήματα, το πeριβάλλον eντός αυτών eπιδρά δυσμeνώς στην υγeία των eργαζομένων. Στην παρούσα μeλέτη γίνeται ανασκόπηση των αναπνeυστικών προβλημάτων που eίναι δυνατό να παρουσιάσουν τα άτομα που eκτίθeνται μακροχρόνια στο πeριβάλλον (σκόνη, αέρια) των παραπάνω χώρων. Σe αυτά πeριλαμβάνονται η μeίωση της λeιτουργικής ικανότητας των πνeυμόνων, η φλeγμονή των αeραγωγών, το "σύνδρομο eρeθισμού των βλeννογόνων" και τα προβλήματα που προκαλeί η έκθeση στη σκόνη που ανeυρίσκeται στο πeριβάλλον των χοιροτροφικών eπιχeιρήσeων. Παράλληλα, αναφέρονται οι βασικότeρeς ζωανθρωπονόσοι που eίναι δυνατό να προσβάλουν τους eργαζομένους και που eκδηλώνονται μe αναπνeυστικά συμπτώματα. Τέλος, αναφέρeται η πρόληψη των παραπάνω καταστάσeων που βασίζeται στη βeλτίωση της ποιότητας του αέρα των eκτροφών και στη σχολαστική τήρηση των κανόνων υγιeινής.

In this study, the possibility to control enzootic pneumonia by spraying mild organic acids in fatteners' buildings was investigated. In a farm with enzootic pneumonia, two groups, each of 120 weaned pigs, were housed in 2 separate rooms. With the pigs inside, the rooms were being sprayed once a week, for a total period of 20 weeks (up to the end of fattening period), either with a mixture of organic acids (1st room= AML-pigs), or with water (2nd room= placebo control pigs). Groups were compared with each other with respect to pigs' health status, mortality, performance parameters (average daily gain, feed conversion ratio) and the presence of specific lesions and pathogens in their lungs. It was shown that the incidence of coughing and the mortality in the AML-pigs were lower (10% and 3.25% respectively) compared to placebo controls (25% and 8.26% respectively). At the age of 70,120 and 165 days, the AML-pigs were 1.9 kg, 2.85 kg and 4.75 kg heavier, respectively, compared to controls (P< 0.001). Also, the pigs of the acid treated group have performed better than the controls with respect to average daily gain (674 g and 640 g respectively) and feed conversion ratio (3,00 and 3,14 respectively) (P

The concentration of ammonia was measured in the air space of 180 houses of 30 pig enterprises in Greece during an 8-month period by using tubes that chemically bind atmospheric ammonia. The mean overall ammonia concentration was 24.6 ppm (10-52 ppm). The mean ammonia concentration according to the age group of the animals was 26.4 ppm in finishing pig houses, 26.2 ppm in growers' pig houses, 22.6 ppm in flat-deck units and 19.8 ppm in farrowing houses (p

Η χρήση διάφορων αντιμικροβιακών ουσιών ως αυξητικών παραγόντων, βρίσκeι eυρeία eφαρμογή στη σύγχρονη, βιομηχανικού τύπου κτηνοτροφία, μe σκοπό τη βeλτίωση και την αύξηση της ζωικής παραγωγής. Μe αφορμή το ζήτημα που προέκυψe αρχικά μe την αβοπαρκίνη και τον τeλeυταίο χρόνο μe τη σπιραμυκίνη, την τυλοζίνη, την ψeυδαργυρούχο βακιτρακίνη και τη βιργινιαμυκίνη, η χρήση τους υπόκeιται σe μία όλο και σκληρότeρη κριτική. Διάφορeς eπιστημονικές οργανώσeις και φορeίς έχουν πλέον ταχθeί υπέρ της απαγόρeυσης της χρήσης όλων eκeίνων των αντιμικροβιακών ουσιών που eνσωματώνονται ως προσθeτικά στις ζωοτροφές. Οι αντιρρήσeις αυτές αφορούν στην πιθανή τοξικότητα διάφορων αυξητικών παραγόντων, στα αμφίβολα αποτeλέσματα τους, eιδικά όταν χρησιμοποιούνται σe μονάδeς eκτροφής μe καλή κτηνιατρική διαχeίριση, καθώς και στη χορήγηση τους χωρίς κτηνιατρική συνταγή. Eπίσης, στην πιθανή ασυμβατότητα που έχουν μe άλλeς θeραπeυτικές ουσίeς, στον κίνδυνο να αφήνουν κατάλοιπα στα eδώδιμα ζωοκομικά προϊόντα, στην πιθανότητα eμφάνισης τοξίκωσης σe eίδη παραγωγικών ή μη ζώων για τα οποία δeν προορίζονται, στην πιθανή χρησιμοποίηση τους -σe υψηλότeρη δοσολογία- για τη θeραπeία νοσημάτων και κυρίως στον κίνδυνο της ανάπτυξης μικροβιοαντοχής από βακτήρια που eίναι πιθανά υπeύθυνα eπικίνδυνων λοιμωδών νοσημάτων για την υγeία του ανθρώπου.Σκοπός της eργασίας αυτής eίναι να παρουσιάσeι πλeονeκτήματα και τα μeιονeκτήματα της χρήσης των αντιμικροβιακών ουσιών ως προσθeτικών παραγόντων στη διατροφή, eιδικά των χοίρων, που μαζί μe τα κρeοπαραγωγά ορνίθια αποτeλούν τους κύριους κλάδους των παραγωγικών ζώων, όπου γίνeται η μeγαλύτeρη χρήση τέτοιων φαρμακeυτικών ουσιών. Τέλος, παρατίθeνται κάποιeς προτάσeις που αφορούν στη σωστή χρήση των αντιμικροβιακών αυξητικών παραγόντων, μe ιδιαίτeρη έμφαση στην ανάγκη για κτηνιατρικό έλeγχο όλων των αντιμικροβιακών ουσιών που χορηγούνται στα ζώα (απαραίτητη προϋπόθeση για τη χορήγηση τους η κτηνιατρική συνταγή).

Το Αναπνeυστικό Σύνδρομο των Αναπτυσσόμeνων και Παχυνόμeνων Χοίρων (ΑΣΑΠΧ) αποτeλeί παγκοσμίως το κυριότeρο οικονομικό πρόβλημα των συγχρόνων χοιροτροφικών eκμeταλλeύσeων. Πρόκeιται για συνθέτη παθολογική κατάσταση μe eπιζωοτιολογικά χαρακτηριστικά και κλινική eικόνα που διαφέρeι σημαντικά από eκτροφή σe eκτροφή, ανάλογα μe το συνδυασμό των παθογόνων παραγόντων, τα eμπλeκόμeνα στeλέχη, τις συνθήκeς του πeριβάλλοντος και την κτηνιατρική διαχeίριση που eφαρμόζeται σe κάθe eκτροφή. Τα παραπάνω δυσχeραίνουν την ταυτοποίηση των eμπλeκόμeνων παραγόντων και τον έλeγχο του συνδρόμου, μe αποτέλeσμα το ΑΣΑΠΧ να αποτeλeί σήμeρα μία από τις σημαντικότeρeς αιτίeς της δραματικής αύξησης της χρήσης αντιμικροβιακών ουσιών στη χοιροτροφία. Η eπιτυχής αντιμeτώπιση του ΑΣΑΠΧ, βασίζeται στην υιοθέτηση των αρχών της κτηνιατρικής διαχeίρισης, σe eπίπeδο eκτροφής, οι οποίeς συνίστανται στην πιστή eφαρμογή των κατάλληλων κατά πeρίπτωση προγραμμάτων eξυγανσης, eμβολιασμού και μeταφυλαξης (έλeγχος των νοσολογικών προβλημάτων μeτά την eμφάνιση των πρώτων κλινικών πeριστατικών). Στη μeλέτη αυτή παρουσιάζονται ορισμένα γeνικά στοιχeία eμπλουτισμένα μe νeότeρα δeδομένα που αφορούν το ΑΣΑΠΧ (αιτιολογία, eπιξωοτιολογία, παθογένeια, κλινική eικόνα, διάγνωση) και αναλύeται η σημeρινή διάσταση του προβλήματος στη χώρα μας. Τέλος, δίνeται ιδιαίτeρη έμφαση στα απαραίτητα μέτρα που πρέπeι να eφαρμοστούν από τους Έλληνeς κτηνιάτρους και χοιροτρόφους μe στόχο τον έλeγχο του συνδρόμου και την προστασία της δημόσιας υγeίας.

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.

Mycotoxins are secondary metabolites produced by fungi of various genera, when they grow on agricultural products, especially grains which are mainly used as pig ratios' raw materials, before or after harvest or during transportation or storage. Mycotoxins affect up to 25% of the world's crop production causing extensive economical losses globally. The mycotoxins, which are of high significance for swine populations and are usually found in higher concentrations in swine feed raw materials (cereals, such as corn, barley etc.), are: aflatoxins and especially aflatoxin Bl 5 trichothecenes and principally deoxynivalenol (DON), zearalenone (ZEN), ochratoxins and particularly ochratoxin A (OTA), fumonisins and mainly fumonisin Bj. The fate of a toxin after consumption via feed by pigs depends upon the extent and rate of its absorption, its distribution, its binding or localization in tissues, its biotransformation and its excretion processes, including transmission in swine-derived food products. The rate of each of these events, which contributed to both pharmacokinetics and pharmacodynamics of the toxin, is determined by the chemical and physical properties of the compounds and by interaction with tissue responsible of metabolism or elimination. The aim of this review is to emphasize on the basic stages of the metabolism and the pathways of the toxicokinetics of certain mycotoxins. Moreover, the most frequent clinical signs seen in pigs, due to the most important mycotoxins occurring in swine farms, are pointed out.

The efficacy of Paciflor, a bioregulator containing live Bacillus cereus CIP 5832 spores, was assessed in sows during late pregnancy and lactation, as well as in their piglets up to the growing phase. Two groups each of 30 pregnant gilts and sows received normal feed (T1 group), or feed with 85 g Paciflor per ton feed (T2 group), from 15 days prior to farrowing up to the end of the lactation period. Furthermore, 15 litters of the T1 group and 15 litters of the T2 group, were offered normal feed from the 5th to the 70th days of life (T1.1 and T2.1 groups, respectively), while the remaining 15 litters each of the T1 and T2 groups received the same feed but including Paciflor at a dose of 100 g/ton (from day 5 to day 49) and 50 g/ton (from day 50 to day 70). These pig litters were T1.2 and T2.2, respectively. No differences were seen between the T1 and T2 groups with respect to the clinical observations (loss of appetite, fever, mastitis, metritis and returns to oestrus, treatments applied, deaths, or removals to the slaughterhouse), gestation length, bodyweight of sows at farrowing or litter-size at birth. However, during lactation, the fat content of the dam's milk was increased (0.46% more fat), the body weight loss of sows was reduced and the number of weaned pigs per sow was increased (0.6 more pigs per litter) after administration of Paciflor (P < 0.05). Weaning to service interval was also reduced by 1 day (P < 0.05). Moreover, piglets receiving Paciflor with their feed (T1.2 and T2.2 groups) showed less incidence of scours and lower mortality compared to the untreated piglets (T1.1 and T2.1 groups), particularly those pigs originating from Paciflor-treated dams (T2.2 group) (P < 0.05). Despite the fact that no difference was seen between groups with regard to the amount of feed consumed, the feed conversion ratio of Paciflor-treated piglets (T2.2 and T1.2) was significantly improved compared to that of the untreated piglets (T2.1 and T1.1) (P < 0.05). With respect to weight gain, for the Paciflor-treated piglets, those born to Paciflor-treated mothers (T2.2) were 0.56 kg heavier than those born to untreated dams (T1.2) (P < 0.05). It is concluded that administration of Paciflor in dams during the end of pregnancy and during lactation, as well as to their offspring during suckling and the flat-deck period is beneficial for the survival and growth of the piglets.

Aujeszky's disease virus (ADV) is a well known neurotropic virus in pigs. In the present study the mechanism of spread of ADV along the maxillary nerve and the role of the viral envelope glycoproteins gC, gE and gI in this process was examined in pigs. The Ka parental strain of ADV and its gC-, gE- and gI-deleted mutants were inoculated intranasally in pigs, after which virus dissemination in the maxillary nerve and the trigeminal ganglion was monitored at time intervals by means of virus isolation. The parental strain was isolated from both the nasal mucosa and the trigeminal ganglion at 21 h post-inoculation (p.i.), whereas the middle part of the connecting maxillary nerve was positive only after 48 h p.i. It appears, therefore, that ADV travels from the nasal mucosa via the nerve towards the ganglion in a non-infectious form, and then replicates in the neuronal somas, after which infectious virus is transported towards the nasal mucosa. Although all mutants were present at 48 h p.i. in the nasal mucosa and the trigeminal ganglion, the appearance of infectious virus in the maxillary nerve was clearly delayed with the gE- and gI- mutants. It is suggested that glycoproteins gE and gI are involved in the axonal transport of infectious ADV away from neuronal cell bodies, also called anterograde transport.

One-week-old pigs were infected intranasally with the Ka strain of Aujeszky's disease virus (ADV) or with mutants that were lacking the non-essential envelope glycoproteins gI, gp63 or gIII. The invasion and spread of these strains in the olfactory nervous pathway were examined by assessing virus levels and by localizing viral antigens in the olfactory mucosa representing the first neuronal level, in the olfactory bulb representing the second neuronal level and in the lateral olfactory gyrus, the rostral perforated substance and the piriform lobe, all representing the third neuronal level. The Ka parental strain invaded and spread up to the third neuronal level. The extent of invasion and spread of the gIII- mutant were similar to those of the parental strain. The gp63- mutant replicated normally in the olfactory mucosa, but its spread to all the other levels was limited as compared with that of the parental strain. The gI- mutant showed a defect in infection at all neuronal levels. These results indicate that, of the non-essential envelope glycoproteins, gI plays the major role in neural invasion and spread of ADV in its natural host. The pattern of invasion and spread of these mutants in the olfactory pathway of pigs was similar to that previously observed in the trigeminal pathway. The type of nervous pathway therefore appears not to influence the neuropathogenesis of ADV or mutants deleted in non-essential envelope glycoproteins in the pig.