Interleukin-6 and chronic inflammation

Abstract

Interleukin (IL)-6 is produced at the site of inflammation and plays a key role in the acute phase response as defined by a variety of clinical and biological features such as the production of acute phase proteins. IL-6 in combination with its soluble receptor sIL-6Ralpha, dictates the transition from acute to chonic inflammation by changing the nature of leucocyte infiltrate (from polymorphonuclear neutrophils to monocyte/macrophages). In addition, IL-6 exerts stimulatory effects on T- and B-cells, thus favoring chronic inflammatory responses. Strategies targeting IL-6 and IL-6 signaling led to effective prevention and treatment of models of rheumatoid arthritis and other chronic inflammatory diseases.

Figure 1

Kinetic of acute-phase protein production. Shown are the characteristic patterns of change that occur in plasma concentrations of some acute phase proteins after a moderate inflammatory stimulus. Reprinted, with permission, from [5]. Copyright ^© 1987 Elsevier.

Figure 2

Possible role played by IL-6 in the shift from acute to chronic inflammation. Stage 1: following acute inflammatory response, IL-6 can bind with sIL-6R. Stage 2: trans-signalling through gp130 leads to monocyte recruitment. Stage 3: prolonged IL-6 leads to neutrophilic apoptosis, phagocytosis and mononuclear accumulation at the site of injury. IL, interleukin; JAK, Janus activated kinase; MCP, monocyte chemoattractant protein; PMN, polymorphonuclear neutrophil; sIL-6R, soluble IL-6 receptor.