Chemokines, inflammation and the immune system.

The chemokine superfamily comprise two families of small secreted proteins that, with the exception of RANTES, beta-TG, and PF-4, are not expressed in resting cells but are rapidly induced in response to various inflammatory and mitogenic stimuli. These proteins function as chemoattractants and activating agents for inflammatory cells. At present, it appears that each of the chemokines have some activities that are unique and many that are overlapping. Important areas that still need to be unravelled are the signal transduction pathways that lead to induction of these genes and the identification of the serpentine receptors and signal transduction pathways that are activated by these proteins. alpha and beta chemokines are implicated as major participants in acute as well as chronic inflammatory reactions, inhibition of haematopoeisis, modulation of angiogenesis, and fibroplasia. Chemokines that act on T lymphocytes presumably influence the recruitment of immunocompetent cells to inflammatory sites. Although there is no evidence that chemokines play a role in the induction of immune reactions, they undoubtedly promote the effector limb of immunity. The likely possibility that chemokines may also contribute to the normal homing and distribution of leukocytes also needs to be evaluated. Although chemokines obviously have major differentiative effects on the functions of target cells, the possibility that they act as costimulants of cell growth also needs more study. Finally, chemokines are attractive targets for the development of new therapeutic agents. Inhibition of their activities may be an effective anti-inflammatory strategy; promoting their activity might enhance wound healing and tissue repair.