Acute phase response is induced by interleukin-6 (IL-6) produced by T cells, macrophages, fibroblasts, endothelial and other cells. IL-6 induces proliferation or differentiation in many cell types including B cells, thymocytes and T cells. IL-6, in concert with TGF-beta, is important for developing Th17 responses. IL-6 binds to IL-6Ralpha and through this association induces gp130 homodimerization. gp130 homodimerization triggers the Jak/Stat cascade and the SHP-2/Erk MAP kinase cascade. IL-6 also forms a complex with an IL-6Ralpha splice variant that is nonmembrane-associated. The IL-6/soluble IL-6Ralpha complex can then activate the gp130 signaling pathway in cells that express gp130 but not IL-6Ralpha. Research studies have shown that IL-6, through increasing expression of proangiogenic VEGF, may also contribute to metastatic breast cancer.
