| Abstract: | IL-10, initially identified as a cytokine synthesis inhibiting factor released by Type 2 T-helper (TH2) cells, is now known to be produced by many cell populations and to play a central role in the regulation of immune and inflammatory responses. Although its principal function is to limit, and ultimately terminate, inflammatory responses by suppressing the activation and effector function of T cells, monocytes and macrophages, IL-10 also affects the growth and/or differentiation of B cells, natural killer cells, cytotoxic and TH2 cells, mast cells and dendritic cells. Importantly, IL-10 appears to be essential for the development and function of a subset of regulatory T cells prominently involved in the maintenance of peripheral tolerance and the control of immune homeostasis. IL-10 exerts these various effects by binding to a cellular receptor (IL10R) composed of at least two subunits. Furthermore, several viral IL-10 homologues that signal through the same receptor complex display immunosuppressive activities similar to those of the mammalian cytokine. Preclinical studies have suggested that the immunosuppressive activities of IL-10 hold potential for the treatment of inflammatory and autoimmune disorders. Recombinant human IL-10 (ilodecakin, TenovilTM, Schering-Plough) has therefore been developed and evaluated by systemic administration in a number of such diseases, including Crohn’s disease, rheumatoid arthritis, psoriasis, chronic hepatitis C and acute pancreatitis. Although the results of these clinical trials have been heterogeneous and disappointing overall, they have provided further insight into the immunobiology of IL-10 and have suggested possible approaches to improve its therapeutic utility. Here, the patent literature associated with IL-10 and its viral homologues is discussed in the light of these recent advances, taking into perspective the experimental evidence that supports future prospects for the therapeutic use of this important class of immunoregulatory cytokines. |
