IL-10 inhibits the proliferation of CD4+ T lymphocytes by inhibiting IL-2 release. It reduces the expression of major histocompatibility (MHC) Class II molecules, the co-stimulatory molecules B7-1 and B7-2 and low affinity IgE receptors (CD23) in antigen-presenting cells, thus effectively blocking allergen presentation by mononuclear cells and dendritic cells to T-cells.38 In addition, IL-10 increases the expression of several anti-inflammatory proteins, including IL-1 receptor antagonist39 and tissue inhibitor of matrix metalloproteinases.40
IL-10 inhibits the release of cytokines from several cell types, including inflammatory cells, epithelial cells and proliferating airway smooth muscle cells.3 ,32 It is very effective in inhibiting eosinophilic inflammation in animal models and this may be through its combined inhibitory effects on IL-5 synthesis, the release of eosinophil chemotactic chemokines (such as eotaxin and RANTES) and through a reduction in eosinophil survival, probably as a result of decreased GM-CSF secretion.41 IL-10 also has an inhibitory effect on IgE-dependent activation of human lung mast cells, with inhibition ofTNF-a and IL-8.42 Surprisingly (and in contrast to results in rodent mast cells) IL-10 also inhibits the release of histamine, suggesting an inhibitory effect on degranulation as well as cytokine synthesis.
A blocking antibody to IL-10 increases the release of cytokines from monocytes and macrophages, suggesting that IL-10 serves as an endogenous feedback inhibitory mechanism to damp down the inflammatory response.38 This has also been demonstrated in vivo in a murine model of allergic inflammation, where an IL-10 blocking antibody increases the airway inflammatory response to allergen.43 Similarly, IL-10 gene knock-out mice have an increased eosinophilic inflammatory response to allergen.44 The kinetics of IL-10 production show a late secretion, which is not maximal until 24 hours after stimulation, whereas the inflammatory genes suppressed by IL-10 are much more rapidly expressed (6-12 hours). This suggests that IL-10 may function as a late "braking" mechanism that prevents persistence of the inflammatory response. Surprisingly, IL-10 knock-out mice fail to develop airway hyperresponsiveness after allergen sensitization, indicating that IL-10 has some unexpected inhibitory action on airway hyperresponsiveness, at variance with previous studies.45 However, when these animals are infected with respiratory syncytial virus they show a skewed Th2 response with exaggerated eosinophilic inflammation.46
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