Modulation of autoimmunity by the latest interleukins (with special emphasis on IL-32)

Abstract

Interleukins (IL) and other cytokines display a number of overlapping abilities to stimulate cells of various lineages and differentiation stages. Most notably, IL-1, tumor necrosis factor (TNF)-alpha, IL-6, IL-15, IL-17, IL-18, IL-21, IL-25, IL-25, IL-31 and IL-32 contribute in concert to pathophysiological events. These include cell death, inflammation, allergy and autoimmunity. Up-regulation of either T helper (TH)1 or TH2 cells is pathogenic, and these subsets downregulate each other. The expression of chemokines/cytokines by endothelial cells is also crucial to autoimmunity by trafficking inflammatory T cells into the central-nervous system. IL-32 (previously termed NK transcript 4), is the newest inflammatory cytokine produced by mitogen-activated lymphocytes, interferon-gamma activated epithelial cells and IL-12, IL-18 and IL-32-activated NK cells. This induces TNF-alpha, IL-1beta, IL-6 and 2 C-X-C chemokine family members involved in several autoimmune diseases. In addition, IL-32 activates arachidonic acid metabolism in peripheral blood mononuclear cells by stimulating the release of prostaglandins. Discovery of this supplementary inflammatory cytokine further complicates the network of inflammation.