Complex cytokine regulation of tissue fibrosis

Tissue fibrosis, a serious and even deadly complication of chronic inflammation and environmental exposures, is regulated by a host of factors including interactions with the extracellular matrix, surface of inflammatory cells, hormones, and an extremely complex and redundant network of profibrotic cytokines. The nature of mechanisms by which cytokines regulate fibrosis is dual - indirect, through attraction of inflammatory cells, and direct, through binding to specific receptors on fibroblasts and stimulating proliferation, collagen production and secretion of autocrine factors. This review focuses on systematizing the direct effects of cytokines on fibroblasts. Understanding of the complexity of the cytokine-driven mechanisms of fibrosis is important for identification of potential molecular targets for future pharmacological interventions in prevention and treatment of tissue fibrosis.