A role for oxygen radicals as second messengers.

All cells seem to produce oxygen radicals. Recent results suggest that small nontoxic amounts of these radicals are released by various cell types in response to stimulation with tumour necrosis factor (TNF), interleukin 1 (IL-1) and phorbol esters, all of which activate a cytoplasmic form of the transcription factor NF-kappa B by releasing an inhibitory protein subunit. Activation is inhibited by agents that remove oxygen radicals, and mimicked by exposure to mild oxidant stress. This article proposes that oxygen radicals act as second messengers for a variety of agents, including the immunomodulatory cytokines TNF and IL-1, in at least one type of regulatory pathway activating NF-kappa B.