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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.

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.

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.

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.

Fibromyalgia (FM) is a disease characterized by chronic widespread pain, fatigue, aches, joint stiffness, depression, cognitive dysfunction, and nonrestorative sleep. In FM, neurotransmission and glial activation can occur with an increase in inflammatory cytokines and involvement of mast cells (MCs) in the skin. FM skin biopsies show an increase in the number of MCs, as well as the production of corticotropin releasing hormone and substance P (SP) by the neurons, which in turn activate MCs to release neurosensitizing proinflammatory substances, such as cytokines, secreted preformed mediators, and lipids, which can exacerbate low-grade inflammation. In fact, certain proinflammatory cytokines are higher in FM and mediate muscle pain, the mechanism of which is not yet clear. MC-derived tumor necrosis factor (TNF) induces nerve growth factor (NGF) and participates in nerve fiber elongation in skin hypersensitivity. IL-37 is an inhibitor of proinflammatory IL-1 family members, which are generated and released by MCs. The goal of this article is to demonstrate that inflammatory cytokines and MC products play a role in FM and that inflammation may be inhibited by IL-37. Here, we propose IL-37 as a cytokine that contributes to improve the pathogenesis of FM by blocking IL-1 family members.

Psoriasis (PS) is an autoimmune disorder characterized by chronic inflammatory skin immune-mediated disease which occurs in 2-4% of the worldwide population. PS is associated with an increased risk of cardiovascular disease and depression, and 30% of PS patients are affected with psoriatic arthritis. PS presents excessive keratinocyte proliferation, abnormal differentiation, and elevated mast cell (MC) number. In PS, there are enhanced type I interferon (IFN), angiogenesis, and over-expression of several proinflammatory cytokines, such as tumor necrosis factor and interleukin (IL)-1 family members generated by several immune cells including MCs. MCs are hematopoietic cells that reside in vascularized tissues, which, upon appropriate activation, release proinflammatory cytokines, an effect worsened by acute stress and PS. In recent years, IL-37 emerged as an anti-inflammatory cytokine which binds to alpha chain of the IL-18 receptor alpha (IL-18Rα) and downregulates MyD88. This effect leads to the inhibition of nuclear factor-κB (NF-κB) and mitogen activation protein kinase, with the suppression of inflammatory response. These observations candidate IL-37 as a potential new therapeutic cytokine for inflammatory disorders including PS.

Atopic dermatitis (AD) is an inflammatory reaction of the skin that can occur in several parts of the body and can be provoked or exacerbated by food and/or environmental compounds. Allergic contact dermatitis (ACD) is a potential enhancer of AD, and an epidermal barrier breaker which induces greater penetration of allergens and other compounds. ACD presents an eczematous rash, red and itchy, with inflammation mediated by cytokines. ACD is an immunological disorder caused by contact with an allergic substance (haptens) that involves immunotoxicity, irritation and inflammation. Mast cells (MCs) are important immune cells that intervene, as effector cells, in allergic and anaphylactic reactions, asthma, autoimmune diseases and cancer. In dermatitis, activated MCs release inflammatory chemical mediators and secrete pro-inflammatory cytokines, including interleukin (IL)-1, TNF, and IL-33. In addition, IL-1 activates MCs to generate a number of cytokines and chemokines, which aggravate inflammation. IL-38 cytokine, an IL-1 family member, is secreted by activated immune cells, including macrophages and lymphocytes, and possesses anti-inflammatory activity. IL-38, by binding IL-36 receptor (IL-36R), provokes suppression of inflammation in many immune diseases. In particular, IL-38 inhibits the generation of IL-1, IL-6 and IL-8 along with other cytokines/chemokines. Here, we hypothesize for the first time that IL-38 may suppresses the inflammatory response in dermatitis, exerting beneficial therapeutic effect.

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.

Systemic mastocytosis in various forms is characterized by mast cell (MC) infiltration of the bone marrow and other internal organs. The most common form is the indolent one with life expectancy similar to the normal population, while the systemic aggressive myeloproliferative type presents serious damage to various organs and is associated with mature and immature atypical mast cells. In systemic mastocytosis patients, MCs could be activated with consequent severe anaphylactic reactions, along with other symptoms. MCs, which are reactive to a variety of external factors such as allergens or other inflammatory or physical stimuli, derive from pluripotent cellular progenitor CD34+ which leaves the bone marrow as CD34+/CD17+ for implantation in the tissues where they reach maturation. MCs participate in the innate and adaptive immune system where they play a role in host defense. Activation of MCs occurs through the binding of IgE to FcεRI receptor, and initiates the phosphorylation and activation of the p38 tyrosine MAP kinase. After various reactions there is a subsequent translation and generation of pro-inflammatory cytokines which are strongly linked to allergic inflammation and mastocytosis. Human cytokine interleukin-37 (IL-37), a unique IL-1β family member, has strong protective and anti-inflammatory properties, influencing cellular metabolism. We investigated the effect of IL-37 on inflammation in mastocytosis and report that the hematopoietic expression of IL-37 can reduce the inflammatory state in this disease. IL-37 limits excessive inflammation, which suggests that IL-37 may be beneficial to the metabolic and inflammatory process and is a candidate as a potential new therapeutic agent.

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

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.

The purpose of this study was to investigate the safety and efficacy of a commercial European porcine reproductive and respiratory syndrome virus (PRRSV)-inactivated vaccine after 18-month use in gilts/sows at a farm with high seroprevalence. In a farrow-to-finish farm with 1100 sows, all sows and gilts were systematically vaccinated with the PRRS-inactivated PROGRESSIS vaccine for a period of 18 months. Farm's reproductive and litter characteristics were longitudinally recorded for this period and historically compared with those of the year prior to vaccination. Serology, employing immunoperoxidase monolayer assay, had confirmed a high prevalence of PRRS-specific antibodies in most age groups within the farm prior to vaccination. Seroprevalence during the experiment ranged between 0% and 100% in weaners and growers, but remained at stable high levels (> 93%) in finishing pigs and gilts throughout all 2-year period of serology measurements. No local or systemic vaccine side effects were noted throughout the trial period. Vaccinations had resulted over time in a significant improvement of sow reproductive performance (e.g. reduction of premature farrowings, abortions and increase of farrowing rate) and litter characteristics (e.g. increase of the number of live born and weaned pigs and decrease of stillborn, mummified, weak and splay-legged piglets). It has also been observed that the higher the degree of immunization of a sow, the better the improvement of her reproductive parameters. Sows after vaccination have shown improved characteristics compared to homoparous sows prior to the application of vaccinations in the farm.

Summary The aim of this trial was to evaluate the effect of in-feed doxycycline (DOXY) on the control of ileitis in weaned piglets. On a farm with a previous history of ileitis outbreaks, 288 piglets at the age of weaning (25 ± 2 days old) were divided into four experimental groups, each group comprising three pens with 24 piglets in each pen. Non-medicated animals served as negative control (NC) group, whereas groups DOXY-50, DOXY-125 and DOXY-250 received doxycycline via feed at 50, 125 and 250 ppm, respectively. Therapy lasted for 14 days followed by an observation period of 28 days. In conclusion, administration of doxycycline at a dose rate of 125 or 250 ppm had beneficial effect compared with the NC group, in terms of the reduction of diarrhoea prevalence, the enhancement of growth performance and the reduction of prevalence of Lawsonia intracellularis in the intestine, as shown either by the PCR method or by specific histopathological examinations. Treatment with 250 ppm of doxycycline for a fortnight interval post-weaning seems to be beneficial leading to better growth rates of piglets not only during treatment period, but also throughout the whole nursery phase.