Cytokine inhibition

The number of known cytokines, as well as the diversity of biological functions, have led to a very complex and often confusing picture of the immunologic and nonimmunologic processes involved. The role of cytokiaes in local or systemic homeostatic mechanisms related to physiological functions may be utilized therapeutically for treatment of cancer and a variety of other diseases (2). Pharmaceutical research and development efforts surrounding lL-1 are typical examples of the cytokine inhibition approach to chronic inflammation research (2). 

IL-10 TH2 cells Macrophages, APC Anti-inflammatory cytokine inhibits cytokine production... 

Glucocorticoids inhibit acquired or cell-mediated immunity. Their effects are mediated via inhibition of genes that code for various cytokines. The cytokines inhibited by glucocorticoids include IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and IFN-y. IL-2 inhibition by corticosteroids is the most crucial effect in immunosuppression, which results in the inhibition of T-cell proliferation and activation of cytolytic T cells. Glucocorticoids also slightly affect humoral immunity by inhibiting B-cell clonal expansion and antibody synthesis, and these effects are mediated via their ability to inhibit B cells ability to express IL-2 and IL-2 receptors. 

PI3 kinase Wortmannin, LY 294002 Inhibit kinase Multiple growth factors and cytokines Inhibit neutrophil (T4) and eosinophil function (B16)... 

Plaque stabilization Reduced CD40 expression and CD40-related activation of vascular cells Reduced leukocyte-endothelial cell interactions Reduced C-reactive protein levels and proinflammatory cytokines Inhibition of LDL oxidation Reduced cytotoxicity of T-lymphocytes Inhibition of proinflammatoiy T helper 1 cell development and augmentation of anti-inflammatoy T helper 2 cell development Reduced oxidized LDL uptake... 

The cytokines IL-2, IL-5 and IL-6 enhance IL-4-induced secretion of IgE by human B lymphocytes (Vercelli etal., 1989 Jabuia et al., 1990), and probably act as permissive stimuli through their non-specific activation of B cells, since there is no evidence that they can induce IgE switching. Several cytokines also inhibit IgE synthesis by human B lymphocytes in vitro. Both IFN7 and IFNa specifically inhibit IgE secretion by B lymphocytes cultured with Epstein-Barr virus (Thyphronitis et al., 1989), although neither of these cytokines inhibits IL-4-dependent induction of increased steady-state concentrations of germline e-chain RNA in B lymphocytes (Gauchat etal., 1990). IL-12 has been reported to reduce IgE synthesis by B lymphocytes stimulated with IL-4 and cortisol (Kiniwa etal., 1992). 

Schwabe M, Cox GW, Bosco MC, et al. Multiple cytokines inhibit interleukin-6-dependent murine hybridoma/plasmacytoma prohferation. Cell Immuno 1996 168 117-21. 

Mucosal biopsy specimens from patients with asthma contain lymphocytes, many of which express surface markers of inflammation. There are two types of T-helper CD4-F cells. Type 1 T-helper (Thl) cells produce IL-2 and interferon-y (IFN-y), both essential for cellular defense mechanisms. Th2 cells produce cytokines (IL-4, -5, -6, -9, and -13) that mediate allergic inflammation. It is known that Thl cytokines inhibit the production of Th2 cytokines, and vice versa. It is hypothesized that allergic asthmatic inflammation results from a Th2-mediated mechanism (an imbalance between Thl and Th2 cells). ... 

Sepsis involves activation of inflammatory pathways, and a complex interaction between proinflammatory and anti-inflammatory mediators plays a major role in the pathogenesis of sepsis. The key proinflammatory mediators include tumor necrosis factor-a (TNF-a), interleukin 1/3 (IL-1/3), and interleukin 6 (IL-6), which are released by activated macrophages. Other mediators that may be important for the pathogenesis of sepsis include interleukin 8 (IL-8), platelet-activating factor (PAF), leukotrienes, and thromboxane A2. " The significant anti-inflammatory mediators include IL-1 receptor antagonist (IL-lra), IL-4, and IL-10. These anti-inflammatory cytokines inhibit the production of the proinflammatory cytokines and down-regulate some inflammatory cells. 

W22. Whicher, J. Cytokine inhibition. Control of receptor appetite (news comment). Nature (London) 344, 584 (1990). 

Adipocytes have profound sensitivity to TNFa, interferons a, P, and y, and interleukins 1, 6, and 11. In general, such cytokines inhibit lipogenesis and triacylglycerol storage by adipocytes, activate lipolysis, and antagonize insulin action. Additionally, many cytokines interfere with proliferation of preadipocytes in 3T3-L1 or 3T3-F442A cell lines and/or... 

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