Inflammatory Interleukins can be classified into pro- and anti-inflammatory interleukins, based largely on their effects on leukocyte function. Pro-inflammatory interleukins induce a Th1, pro-inflammatory phenotype in lymphocytes, while anti-inflammatory interleukins induce a shift to a Th2 profile, with attenuation of pro-inflammatory cytokine expression and concomitant increase in anti-inflammatory cytokine expression.
Anti-inflammatory interleukins, are cytokines that play great roles in counterbalancing the pro-inflammatory response in various infectious diseases. Major anti-inflammatory interleukins include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-13, IL-19 and IL-35.
Despite sharing receptor components with IL-2, Interleukin-4 (IL-4) promotes a Th2 response in lymphocytes. IL-4 negatively regulates production of pro-inflammatory cytokines in macrophages and T cells.
Although recognized as a T cell growth factor, IL-9 exerts a Th2 inflammatory response in these cells, and suppresses expression of TNFα, IFNγ, with a concurrent up regulation of IL-10. IL-9 is also implicated in playing a role in airway smooth muscle inflammation, and asthma.
IL-10 is considered a prototypical anti-inflammatory cytokine, and is the most widely studied of the anti-inflammatory interleukins.
IL-11 shares considerable sequence homology to the potent pro-inflammatory cytokine IL-6, and even shares a common gp130 receptor subunit with IL-6. However, despite these similarities, IL-11 does promote a T cell phenotypic switch from Th1 to Th2, and also down-regulates NF-κB activity in both immune and vascular cells.
Pro-inflammatory interleukins are a series of immune regulatory molecules (cytokines) and are involved in the up-regulation of inflammatory reactions. Various pro-inflammatory interleukins such as IL-1, IL-8, IL-17 and IL-23 have been identified to be angiogenic, and increase EC migration, cord-like structure organization, and MMP production.
The main effects of IL-17 are pro-inflammatory, including production by macrophages of pro-inflammatory mediators (TNF-α, IL-1ß, IL-6, IL-12, and PGE2) and production by fibroblasts and keratinocytes of IL-6 and IL-8.
Injecting recombinant IL-17 into joints has been reported to cause joint inflammation and cartilage destruction. In the mouse CIA model, injection of an adenovirus encoding IL-17 increases disease severity and induces production of the RANK ligand through mechanisms independent from IL-1.
Administration of anti-inflammatory cytokines decreases the activity of IL-17. Thus, IL-4 and IL-13 inhibit the production of IL-17 by ex-vivo rheumatoid synovium explants. Similarly, IL-17 levels within joints decrease when mice with CIA are given IL-4.
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