Controlling the production of interleukin-1 and tumor necrosis factor in disease.

Interleukin 1 (IL-1), either IL-1 alpha or IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) are primarily inflammatory cytokines. The most studied drugs that suppress the production of IL-1 and TNF are corticosteroids, which inhibit the transcription of IL-1, TNF, and other cytokines. Nonsteroidal compounds that are cyclooxygenase-lipoxygenase inhibitors are called dual inhibitors. Other agents that suppress IL-1 and TNF are termed cytokine-suppressing antiinflammatory drugs (CSAIDs). The mechanism by which CSAIDs act appears to be through their ability to bind a mitogen activating protein (MAP) kinase that is needed for translation of cytokine mRNAs. The importance of lipoxygenase products in the production of IL-1 has been shown. IL-4, IL-10, and IL-3 suppress gene expression and synthesis of IL-1 and TNF. We carried out a randomized, double-blind, placebo-controlled trial in healthy human volunteers using a single intravenous injection of IL-10. These studies indicate that IL-10 may be useful for suppressing inflammatory cytokine production in a variety of diseases.