Role of cytokines and cytokine therapy in wound healing and fibrotic diseases

Cytokines are critical to a myriad of fundamental homeostatic and pathophys iological processes such as fever, wound healing, inflammation, tissue repa ir and fibrosis. They play important roles in regulating cell function such as proliferation, migration, and matrix synthesis. It is the balance or th e net effect of the complex interplay between these mediators, which appear s to play a major role in regulating the initiation, progression and resolu tion of wounds. Wound healing involves a complex process including inductio n of acute inflammation by the initial injury, followed by parenchymal and mesenchymal cell proliferation, migration, and activation with production a nd deposition of extracellular matrix. Failure to resolve or abnormal wound healing results in fibrosis. The latter process involves similar cellular interactions via complex cytokine networks, which result in extensive remod eling with heightened extracellular matrix production and their abnormal de position in the tissue. Various cytokines, both promoting and inhibiting fi brogenesis, have been implicated in the pathogenesis of fibrosis and wound healing. Recent progress in understanding the mechanisms underlying the pat hogenesis of fibrosis leads us to expect that inhibitors of pro-fibrogenic cytokines and growth factors may be useful as novel therapeutic agents in c ontrolling undesirable fibrosis. In this review, the role of cytokines in w ound healing and fibrosis will be summarized and highlighted with more deta iled discussion reserved for the possible points of therapeutic attack in p ulmonary fibrosis. In this review, the major cytokines that are in current clinical use will be also discussed. In addition, advances in the applicati on of novel cytokines and anti-cytokines for accelerating wound healing and attenuating fibrosis both at the experimental and the clinical trial level s will be discussed.