IL-6 is a cytokine that plays multiple roles in inflammation, acute phase response, hematopoiesis, and regulation of the immune system. IL-6 binds to IL-6Rα with nanomolar affinity. The complex IL-6/IL-6Rα triggers dimerization of gp130, in which the receptor-ligand interaction induces the signal transduction though the JAK/STAT pathway. gp130 is also a receptor subunit for IL-11, CNTF, LIF, OSM, CT-1, CLC, and IL-27. gp130 is ubiquitously expressed in different types of cells. Nevertheless, gp130 does not bind IL-6 nor IL-6Rα, thus cells only expressing gp130 are unresponsive to IL-6. IL-6Rα and gp130 have soluble forms. Soluble IL-6Rα (sIL-6Rα) is generated by two mechanisms: by shedding from the membrane and by translation of a differentially spliced RNA. Cells expressing only gp130 can be responsive to the complex of IL-6/sIL-6Rα, and this process has been named trans-signaling. Inflammatory processes induce the shedding of IL-6R from neutrophils, and the complex IL-6/sIL-6Rα activates endothelial cells to produce MCP-1, which attracts monocytes. Soluble gp130 (sgp130) can be found in a ternary complex with IL-6 and sIL-6Rα, and it has been suggested to be the natural inhibitor of sIL-6Rα. Increased levels of sIL-6Rα have been detected in colitis, arthritis, and idiopathic pulmonary fibrosis. In vivo neutralization of sIL-6Rα attenuated pulmonary fibrosis in mice.