Cytokine and anti-cytokine strategies in inflammatory reaction modulation

Evidence of the importance of a cytokine cascade in the induction and control of the inflammatory reaction is increasing. Although cytokines are required in the inflammatory process in response to infection or injury, their overproduction, particularly that of interleukin-1 (IL-1) and tumor necrosis factor (TNF), can lead to local/systemic pathology. Selective inhibition of the synthesis or of the action of specific cytokines may be of therapeutic benefit. Various strategies for blocking IL-1 and TNF activities have been presented. While selective inhibition of cytokine synthesis is still in the early experimental phase, specific blockade of soluble cytokine action following synthesis and release from cells is undergoing preliminary clinical trials in humans. Animal data suggest that antimonoclonal therapy such as monoclonal antibodies to TNF, IL-1 receptor antagonists or soluble receptors to TNF and IL-1 can be effective in the modulation of the inflammatory reaction. Modulation of the cytokine network in some diseases might also include the use of anti-inflammatory cytokines. Nonetheless, the possibilities of side effects due to impaired host-defense mechanisms with the IL-1 or TNF blockade must also be taken into consideration.