INVOLVEMENT OF INTERLEUKIN-1 AND LIPOCORTIN-1 IN ISCHEMIC BRAIN-DAMAGE

The cytokine interleukin-1 (IL-1) is synthesised within the brain and acts as a mediator of host defence responses to disease and injury. Se veral of these central actions of IL-1 are inhibited by an endogenous calcium and phospholipid binding protein, lipocortin-1. Synthesis of I L-1 and lipocortin-1 in the brain is markedly increased by neuronal da mage, and inhibition of the actions of endogenous IL-1 by central inje ction of IL-1 receptor antagonist in the rat significantly inhibits is chaemic and excitotoxic brain damage. Lipocortin-1 appears to act as a n endogenous neuroprotective agent that markedly attenuates ischaemic and excitotoxic damage. In contrast, inhibition of the actions of lipo cortin-1 by injection of neutralising antiserum exacerbates both forms of neurodegeneration. The mechanisms underlying these effects of IL-1 and lipocortin-1 are largely unknown, but are probably independent of changes in body temperature. Actions of these molecules on corticotro phin releasing factor, arachidonic acid, excitatory amino acids, and n itric oxide, and the possible involvement of these factors in brain da mage are discussed.