Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings.

There is an emerging concept that the net biological response of pro and anti-inflammatory cytokines affects the outcome of certain diseases. In inflammatory diseases, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are produced and function primarily as pro-inflammatory cytokines. In addition, other cytokines such as IFN gamma, IL-12 and IL-18 are also produced and affect the production and cellular response to IL-1 and TNF. Biologically, IL-1 and TNF are closely related, although the respective structures and the specific receptors for IL-1 and TNF are clearly distinct. IL-1 and TNF are truly pleiotropic cytokines and are active in the low pM and fM range. Because of their multiple pro-inflammatory properties, these cytokines contribute to disease. Most of our knowledge on IL-1 and TNF are derived from experiments in which either humans or animals have been injected with the cytokine or added to cells in vitro. However, in models of inflammation where several cytokines are produced, specific blockade of either IL-1 or TNF or both results is a reduction in the severity of the inflammation. These latter data therefore implicate IL-1 and TNF as primary cytokines involved with inflammation. Moreover, IL-1 and TNF act synergistically in nearly every in vitro and in vivo model of inflammation. This review will focus on IL-1 and TNF as cytokines of strategic importance to the initiation and progression of inflammation. In addition, this review examines the effects of anti-inflammatory cytokines which non-specifically reduce the production and activity of IL-1 and TNF.