Down-regulation of cytokine action

The study of cytokines that regulate all areas of cellular communication has expanded over the past few years. The control and modulation of the complex network of cytokine action remains an area of intense interest. Agents that will modulate cytokine signal transduction at the cellular level will assist in the understanding of the molecular basis of cytokine cellular activation and in the design of drugs for the management of clinical disease. Recent work has demonstrated the existence of complex mechanisms of negative regulation of cytokine action. New methods utilizing isolated protein products that participate in immunomodulation may prove useful for clinical regulation of the host response to cytokine up-regulation. Currently, most interest in soluble cytokine receptors, natural cytokine inhibitors, genetically engineered cytokine antagonists and single or combinations of anti-inflammatory cytokines has focused on the possibility that they may become standard pharmacological agents for the treatment of inflammatory complications of clinical disease. Specifically, TNF and IL-1 inhibitors and the cytokines IL-10 and TGF-beta, alone or in combination may be effective for the inhibition of severe clinical inflammation. Soluble receptors for other cytokines such as IL-6 may prove to be carrier proteins that enhance cytokine action and will require cautious investigation. Because most cytokines are pleiomorphic in their activities, down-regulation through the utilization of direct inhibitors or anti-inflammatory cytokines may cause immunosuppression, making the host susceptible to opportunistic infection. Selective and short-term inhibition of inflammatory cytokine action may be necessary to prevent unwanted clinical side-effects.