IL-10, initially designated cytokine synthesis inhibitory factor (CSIF), was originally identified as a product of murine T helper 2 (Th2) clones that inhibited the cytokine production by Th1 clones which are dependent upon stimulation with antigen in the presence of antigen presenting cells (APC). The human homologue of murine IL-10 was subsequently cloned by cross-hybridization. Human and murine IL-10 are 81% and 73% homologous at the nucleotide and amino acid level, respectively. Both murine and human IL-10 are also highly homologous with a previously uncharacterized open reading frame in the Epstein-Bar virus (EBV) genome, BCRF1. The BCRF1 gene product is now designated viral IL-10. Murine IL-10 is produced by Th2 cells, activated fetal thymocytes, macrophages, keratinocytes, and LY-1+ (CD5+) and normal B cells. Human IL-10 has cross-species actvities and is active on mouse cells. Murine IL-10 is species-specific and does not act on human cells. Porcine IL-10 is 71% and 78% homologous with mouse and human IL-10, respectively.
IL-10 is a pleiotropic cytokine that can exert either immunostimulatory or immunosuppressive effects on a variety of cell types. It is a potent immunosuppressant of macrophage functions. In vitro, IL-10 can inhibit the accessory function and antigen-presenting capacity of monocytes by, among other effects, downregulating class II MHC expression. Thus, IL-10 can inhibit monocyte/macrophage-dependent, antigen stimulated cytokine synthesis (especially IFN-gamma ) by human PBMNC and NK, and mouse Th1 cells. Additionally, IL-10 is a potent inhibitor of monocyte/macrophage activation and its resultant cytotoxic effects. As an immunostimulatory cytokine, IL-10 can act on B cells to enhance their viability, cell proliferation, Ig secretion, and class II MHC expression. Aside from B lymphocytes, IL-10 is also a growth co-stimulator for thymocytes and mast cells, as well as an enhancer of cytotoxic T cell development.
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