Interleukin6

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune responses, inflammation, and hematopoiesis. It is produced by T cells, macrophages, dendritic cells, endothelial cells, and fibroblasts in response to infections and tissue injury.

IL-6 signals through a receptor complex comprising the IL-6 receptor (IL-6R) and the signal transducer gp130. Classic signaling uses membrane-bound IL-6R, while trans-signaling employs soluble IL-6R, enabling activity on cells that lack IL-6R. gp130 is widely expressed, allowing broad responsiveness to IL-6.

Activated signaling pathways include JAK/STAT3, MAPK, and PI3K-Akt, which drive transcriptional programs that regulate inflammation, cell survival, and differentiation.

Biologically, IL-6 promotes production of acute-phase proteins by the liver, supports B cell differentiation into plasma cells, and influences T cell responses, including Th17 differentiation. It also participates in fever and metabolic regulation during illness.

Clinical relevance: IL-6 levels rise in infection and inflammatory diseases and serve as a biomarker of inflammation. Dysregulated IL-6 signaling is implicated in autoimmune disorders and cancer. Therapeutically, monoclonal antibodies targeting IL-6 or IL-6R are approved for several conditions, including tocilizumab and sarilumab (IL-6R inhibitors) and siltuximab (anti-IL-6).

Genetics and structure: the IL6 gene encodes a secreted glycoprotein; the precursor contains a signal peptide that directs secretion. IL-6 is a member of the broader IL-6 cytokine family and was historically described as a B cell differentiating factor.