INHIBITION OF INTERLEUKIN-1-BETA-INDUCED PYRESIS IN THE RABBIT BY PEPTIDE-204-212 OF LIPOCORTIN-5

The intracerebroventricular administration of interleukin-1 beta (12.5 ng/kg) in rabbits caused a prompt rise of prostaglandin E(2) concentr ation (+ 632.6 +/- 243.9%) in the cerebrospinal fluid followed by hype rthermia (+1.61 +/- 0.14 Delta degrees C). The intracerebroventricular administration of an anti-inflammatory nonapeptide (amino acids 204-2 12, SHLRKVFDK) derived from lipocortin 5, thereafter referred to as li pocortin 5-(204-212)-peptide, inhibited in a significant manner both t he increase in cerebrospinal fluid [prostaglandin E(2)] and the febril e response induced by the cytokine. This inhibitory effect is probably due to interference by the peptide with phospholipase A(2) activity. A control peptide (FKRVHDLKS) formed by the same amino acids in a rand omly shuffled sequence had no effect. These results show that, in addi tion to the anti-inflammatory effect previously reported, the peptide 204-212 of lipocortin 5 possesses, like glucocorticoids, anti-pyretic activity. The research on lipocortin-derived peptides may lead to the development of novel anti-inflammatory and anti-pyretic compounds.