Termination of acute-phase response: role of some cytokines and anti-inflammatory drugs.

1. The acute-phase response is triggered by changes in intracellular mediators that activate stress-sensitive kinases and transcription factors controlling the synthesis of proinflammatory cytokines such as TNF-alpha, IL-1, IL-8 or IFN-gamma. 2. Natural extinguishing of acute-phase response occurs due to short half-lives of inflammatory mediators and production of anti-inflammatory cytokines such as IL-10, IL-4, IL-13, TGF-beta and some others. 3. Excess proinflammatory cytokines are removed by soluble cytokine receptors and receptor antagonists. 4. Synthesis of proinflammatory mediators and cytokines can be blocked by glucocorticoids, some nonsteroidal anti-inflammatory drugs suppressing cyclooxygenase and by specific inhibitors of cytokine induction. 5. The most promising approach in effective termination of acute-phase response appears to be a combined use of anti-inflammatory cytokines and specific drugs.