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Cytokines are pleiotropic polypeptides that control the development of and responses mediated by immune cells. Cytokine classification predominantly relies on [1] the target receptor(s), [2] the primary structural features of the extracellular domains of their receptors, and [3] their receptor composition. Functionally, cytokines are either pro-inflammatory or anti-inflammatory, hematopoietic colony-stimulating factors, developmental and would healing maintaining immune homeostasis. When the balance in C can form complex networks amongst themselves that may affect the homeostasis and diseases. Cytokines can affect resistance and susceptibility for many diseases and their availability in the host cytokine production and interaction is disturbed, immunopathogenesis sets in. Therefore, cytokine-targeting bispecific, and chimeric antibodies form a significant mode of immnuo-therapeutics Although the field has grown deep and wide, many areas of cytokine biology remain unknown. Here, we have reviewed these cytokines along with the organization, signaling, and functions through respective cytokine-receptor-families. Being part of the special issue on the Role of Cytokines in Leishmaniasis, this review is intended to be used as an organized primer on cytokines and not a resource for detailed discussion- for which a two-volume Handbook of cytokines is available- on each of the cytokines. Priming the readers on cytokines, we next brief the role of cytokines in Leishmaniasis. In the brief, we do not provide an account of each of the involved cytokines known to date, instead, we offer a temporal relationship between the cytokines and the progress of the infection towards the alternate outcomes- healing or non-healing- of the infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Random mutations leading to loss of cell cycle control is not a rare occurrence in an organism but the mutated cells are recognized and eliminated preventing the development of a tumor. These potentially tumorigenic cells release damage-associated molecular patterns (DAMPs), which are recognized by toll-like receptors (TLRs) on macrophages and dendritic cells. The initial TLR-DAMP interactions lead to different responses such as altered antigen presentation and cytokine release that directly affect T cell activation and removal of the tumorigenic cells. The indirect effects of TLR-DAMP interaction include chemokine-directed altered T cell trafficking, angiogenesis for both T cell infiltration and tumor cell metastasis, and alteration of intra-tumoral milieu contributing to the development of tumor cells heterogeneity. Thus, the initial TLR-DAMP interaction has a set of local effects that modulate tumor cell growth and heterogeneity and a disseminating set of central effects that dynamically affect T cell trafficking and functions. Herein, we argue that the DAMP-TLR-cytokine axis in the tumor microenvironment serves as the mainstay that orchestrates and regulates the pro- and anti-tumor elements which dynamically interact between themselves eventuating in tumor regression or growth. The knowledge of this TLR-based immuno-surveillance framework is a key to developing a novel immunotherapy against cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Suppressor of cytokine signalling (SOCS) proteins bind to certain cytokine receptors, Janus kinases and signalling molecules to regulate signalling pathways, thus controlling immune and inflammatory responses. Dysregulated expression of various types of SOCS molecules was indicated in multiple types of allergic diseases. SOCS1, SOCS2, SOCS3, SOCS5, and cytokine‐inducible SH2 domain protein (CISH) can differentially exert anti‐allergic impacts through different mechanisms, such as suppressing Th2 cell development and activation, reducing eosinophilia, decreasing IgE production, repressing production of pro‐allergic chemokines, promoting Treg cell differentiation and activation, suppressing Th17 cell differentiation and activation, increasing anti‐allergic Th1 responses, inhibiting M2 macrophage polarization, modulating survival and development of mast cells, reducing pro‐allergic activity of keratinocytes, and suppressing pulmonary fibrosis. Although some anti‐allergic effects were attributed to SOCS3, it can perform pro‐allergic impacts through several pathways, such as promoting Th2 cell development and activation, supporting eosinophilia, boosting pro‐allergic activity of eosinophils, increasing IgE production, enhancing the expression of the pro‐allergic chemokine receptor, reducing Treg cell differentiation, increasing pro‐allergic Th9 responses, as well as supporting mucus secretion and collagen deposition. In this review, we discuss the contrasting roles of SOCS proteins in contexts of allergic disorders to provide new insights regarding the pathophysiology of these diseases and possibly explore SOCS proteins as potential therapeutic targets for alleviating allergies. [ABSTRACT FROM AUTHOR]

Multiple pathogen‐associated molecular patterns (PAMPs) on a pathogen's surface imply their simultaneous recognition by the host cell membrane‐located multiple PAMP‐specific Toll‐like receptors (TLRs). The TLRs on endosomes recognize internalized pathogen‐derived nucleic acids and trigger anti‐pathogen immune responses aimed at eliminating the intracellular pathogen. Whether the TLRs influence each other's expression and effector responses—termed TLR interdependency—remains unknown. Herein, we first probed the existence of TLR interdependencies and next determined how targeting TLR interdependencies might determine the outcome of Leishmania infection. We observed that TLRs selectively altered expression of their own and of other TLRs revealing novel TLR interdependencies. Leishmaniamajor—an intra‐macrophage parasite inflicting the disease cutaneous leishmaniasis in 88 countries—altered this TLR interdependency unfolding a unique immune evasion mechanism. We targeted this TLR interdependency by selective silencing of rationally chosen TLRs and by stimulation with selective TLR ligands working out a novel phase‐specific treatment regimen. Targeting the TLR interdependency elicited a host‐protective anti‐leishmanial immune response and reduced parasite burden. To test whether this observation could be used as a scientific rationale for treating a potentially fatal L. donovani infection, which causes visceral leishmaniasis, we targeted the inter‐TLR dependency adopting the same treatment regimen. We observed reduced splenic Leishman–Donovan units accompanied by host‐protective immune response in susceptible BALB/c mice. The TLR interdependency optimizes TLR‐induced immune response by a novel immunoregulatory framework and scientifically rationalizes targeting TLRs in tandem and in sequence for redirecting immune responses against an intracellular pathogen. [ABSTRACT FROM AUTHOR]

Despite chlorogenic acid (CGA) being widely present in nature, particularly in the human diet, there is very little information regarding its pharmacological activities. The present investigation was carried out to investigate the antiarthritic activities of this compound in adjuvant induced-arthritis in male Wistar rats, and to explore the underlying mechanisms of actions in view of immunological responses. We observed that CGA effectively controlled the total (CD3) and differentiated (CD4 and CD8) T cells count at the dose of 40 mg/kg. We also assessed the effect on co-stimulatory molecules (CD28, CD80/86) and found that CGA efficiently suppressed CD80/86 but failed to bring any changes in the CD28 count, whereas ibuprofen (standard drug) resulted in highly significant inhibition of both. We next examined the effect on CD4+ T cells specific Th1/Th2 cytokines by flow cytometry and observed that CGA suppressed the Th1 cytokines in a highly significant manner but elevated Th2 cytokines with dose dependence. Results of the present investigation suggest that CGA is a potent antiarthritic agent. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Argyrolobium roseum (Papilionaceae) is a sexually reproducing, rare, annual herb that grows in tropical and sub-temperate tracts of the north-western Himalayan region of the Indian subcontinent. The present investigation was carried out to study the immunomodulatory properties of this herb in well established experimental models. For preliminary pharmacological activity evaluation, we first studied the effect of aqueous fraction (KA-134) of A. roseum on humoral and cell mediated immune responses and found that KA-134 dose dependently suppressed the antibody titre and delayed type hypersensitivity reaction. Inspired by the results, we further fractionated KA-134 which yielded pinitol, which on further immunomodulatory studies resulted in highly significant inhibition of CD3, CD19, CD4 and CD8 count and Th1/Th2 cytokines expression in splenocytes. Pinitol was also found to be safe when tested against cell viability assays (in vitro and in vivo). Based on the data, it can be suggested that pinitol is a potent and non-toxic immunosuppressor, which can be further explored for the development of potent immunosuppressor. [ABSTRACT FROM AUTHOR]

Abstract: Many herbs and spices are known to modulate the immune system and have been shown to restore the immunity in immuno-compromised individuals. Spices generally used to increase the taste and flavor of food also has the history of usage as an ayurvedic medicine. Therefore to explore the health modulating effects of Cuminum cyminum and to identify the active compound, immunomodulatory properties were evaluated using flowcytometry and ELISA in normal and immune-suppressed animals. C. cyminum and compound 1 stimulated the T cells and Th1 cytokines expression in normal animals. Swiss albino mice subjected to Cyclosporine-A induced immune-suppression were dosed orally with C. cyminum (25, 50, 100 and 200mg/kg) on consecutive days. The results showed that administration significantly increased T cells (CD4 and CD8) count and Th1 predominant immune response in a dose dependent manner thereby suggesting immunomodulatory activity through modulation of T lymphocytes expression. In restraint stress induced immune-suppressed animals, compound 1 countered the depleted T lymphocytes, decreased the elevated corticosterone levels and size of adrenal glands and increased the weight of thymus and spleen. Based on the data we may conclude that C. cyminum is a potent immunomodulator and may develop as a lead to recover the immunity of immuno-compromised individuals. [Copyright &y& Elsevier]

Objective: To investigate the immunosuppressive potential of Pluchea lanceolata 50% ethanolic extract (PL) and its bioactive chloroform fraction (PLC). Materials and Methods: Preliminary screening of the Pluchea lanceolata 50% ethanolic extract (PL) was carried out with basic models of immunomodulation, such as, the humoral antibody response (hemagglutination antibody titers), cell-mediated immune response (delayed-type hypersensitivity), skin allograft rejection test, in vitro (C. albicans method), and in vivo phagocytosis (carbon clearance test). The extract was then fractionated with chloroform, n-butanol, and water to receive the respective fractions by partitioning. These fractions were employed for flow cytometry to study the T-cell specific immunosuppressive potential of these fractions. Results: Oral administration of PL at doses of 50 to 800 mg/kg in mice, with sheep red blood cells (SRBC) as an antigen, inhibited both humoral and cell-mediated immune responses, as evidenced by the production of the circulating antibody titer and delayed-type hypersensitiviy reaction results, respectively, and the immune suppression was statistically significant (P < 0.01) in Balb/C mice. PL also decreased the process of phagocytosis both in vitro (31.23%) and ex vivo (32.81%) and delayed the graft rejection time (30.76%). To study the T-cell-specific activities, chloroform, n-butanol, and water fractions from P. lanceolata were tested for T-cell specific immunosuppressive evaluation, wherein only the chloroform fraction (PLC) showed significant (P < 0.01) suppression of CD8+ / CD4+ T-cell surface markers and intracellular Th1 (IL-2 and IFN-γ) cytokines at 25 - 200 mg/kg p.o. doses. PLC, however, did not show significant suppression of the Th2 (IL-4) cytokine. Conclusion: The findings from the present investigation reveal that P. lanceolata causes immunosuppression by inhibiting Th1 cytokines. [ABSTRACT FROM AUTHOR]

The premise of the study was to investigate the effect of Acetyl-11-Keto-β-Boswellic acid (AKBA) on pro- inflammatory cytokines in inflamed rat knee joint. AKBA showed a significant dose dependent decrease in expression of TNF-α in in vitro.study on LPS activated rat neutrophils that were followed by study on its effect on pro-inflammatory cytokines produced in the synovial fluid in the knee joints of rat as a result of inflammatory effect-induced by intra-articular injection of bacterial lipopolysaccharide (LPS). AKBA at 4 and 8 mg/kg oral dose suppressed the pro-inflammatory cytokines in synovial fluid (in vitro), thereby showing potent inhibitory properties and usefulness in the treatment of inflammation and associated diseases as these cytokines play a major role in furthering the ill effects associated with inflammation. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) recognize the pathogen-associated molecular patterns (PAMPs) and induce host-protective immune response. The role of the profilin-recognizing TLR11/TLR12 in Leishmania infection is unknown. Herein, we report that TLR11/ TLR12 expression increases in virulent L. major -infected macrophages but is prevented by miltefosine, an anti-leishmanial drug. While lipohosphoglycan (LPG) increases, LPG or TLR2 blockade prevents, the heightened TLR11/TLR12 expression. LPG-TLR2 interaction triggers MyD88- and TIRAP-mediated signaling enhancing ERK-1/2 activation and increased production of IL-10 that promotes TLR11/TLR12 expression. Profilin expression was higher in the virulent L. major and L. donovani parasites than that observed in the avirulent parasites. TLR11 or TLR12 silencing reduces parasite burden and increases IFN-γ, but reduces IL-4, production indicating that TLR11 and TLR12 play a pro-leishmanial role. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the T cell inhibition potential of 50% ethanol extract of Cyperus scariosus (CS) and its bioactive chloroform fraction (CSC). Methods: The preliminary screening of the extract was carried out by humoral antibody response and delayed-type hypersensitivity models employing sheep red blood cells (SRBC) as the antigen. Further, the extract was studied by skin allograft rejection test, and phagocytosis - in vitro and ex vivo - by C. albicans method and carbon clearance test, respectively. The extract was fractionated with chloroform, n-butanol and water, and then used to investigate the T-cell specific immunosuppressive potential of these fractions by flow cytometry. Results: On p.o. administration, CS inhibited both humoral and cell-mediated immune responses significantly (p < 0.01) by suppressing primary (26.8 %) and secondary (29.7 %) antibody titres, and also inhibited cell-mediated delayed type hypersensitivity (DTH) immune response (45.9 %) at 600 mg/kg dose, phagocytosis - both in vitro (37.4 %) and ex vivo (37.8 %) - and delayed the graft rejection time (45.8%), thus confirming marked immunosuppression. Out of the three isolated fractions, only the chloroform fraction significantly (p < 0.01) suppressed CD8+/ CD4+ T cell surface markers (14.0/25.3 %) and intra-cellular Th1 cytokines, viz, IL-2 (34.4 %), and IFN-γ (34.7 %), compared to cyclosporine-A (5), a standard T cell inhibitor (53.6 %) which was given to Balb/C mice at 200 mg/kg dose. CSC did not significantly (p < 0.01) suppress Th2 (IL-4) system. Conclusion: The findings from this investigation reveal that C. scariosus causes immunosuppression by inhibiting Th1 cytokines. [ABSTRACT FROM AUTHOR]