title: Involvement of interleukin-1 and lipocortin-1 in ischaemic brain damage.
abstract: The cytokine interleukin-1 (IL-1) is synthesised within the brain and acts as a mediator of host defence responses to disease and injury. Several of these central actions of IL-1 are inhibited by an endogenous calcium and phospholipid binding protein, lipocortin-1. Synthesis of IL-1 and lipocortin-1 in the brain is markedly increased by neuronal damage, and inhibition of the actions of endogenous IL-1 by central injection of IL-1 receptor antagonist in the rat significantly inhibits ischaemic and excitotoxic brain damage. Lipocortin-1 appears to act as an endogenous neuroprotective agent that markedly attenuates ischaemic and excitotoxic damage. In contrast, inhibition of the actions of lipocortin-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 corticotrophin releasing factor, arachidonic acid, excitatory amino acids, and nitric oxide, and the possible involvement of these factors in brain damage are discussed.
authors.affiliation: Department of Physiological Sciences, University of Manchester, England.
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: J K
authors.initials: JK
authors.lastname: Relton
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*
chemical_list: D017305:Annexin A1; D007375:Interleukin-1