IL-6 is a multifunctional cytokine that can regulate various immune and inflammatory responses. Several studies have suggested a crucial role for IL-6 in angiogenesis. The use of mice deficient in IL-6 (–/–) demonstrated a critical role for this protein in a mouse model of lung angiogenesis. IL-6 has been shown to cause proliferation and migration of systemic endothelial cells in culture. The classical responsiveness to IL-6 is governed by a receptor complex consisting of two membrane-bound subunits, an 80-kD cognate -chain (IL-6R ), and a ubiquitously expressed 130-kD β-chain receptor (gp130) which acts as the universal signal-transducing element for all IL-6 family cytokines. Alternatively, IL-6 regulation of leukocyte trafficking relies upon signaling via its soluble IL-6R (termed IL-6 trans-signaling). IL-6 plays a major role in regulating neutrophil clearance during acute peritoneal inflammation; as a result of specific down-regulation of neutrophil-attracting chemokine (CXCL1/KC) production. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3(+) Treg differentiation by inhibition of TGF-beta induced Foxp3 and induction of RORgammat, a Th17 lineage-specific transcription factor.