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 E2 concentration (+ 632.6 +/- 243.9%) in the cerebrospinal fluid followed by hyperthermia (+ 1.61 +/- 0.14 delta degrees C). The intracerebroventricular administration of an anti-inflammatory nonapeptide (amino acids 204-212, SHLRKVFDK) derived from lipocortin 5, thereafter referred to as lipocortin 5-(204-212)-peptide, inhibited in a significant manner both the increase in cerebrospinal fluid [prostaglandin E2] and the febrile response induced by the cytokine. This inhibitory effect is probably due to interference by the peptide with phospholipase A2 activity. A control peptide (FKRVHDLKS) formed by the same amino acids in a randomly shuffled sequence had no effect. These results show that, in addition 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.
Palmi
M
M
Institute of Pharmacological Sciences, University of Siena, Italy.
Frosini
M
M
Sgaragli
G P
GP
Becherucci
C
C
Perretti
M
M
Parente
L
L
D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004347:Drug Interactions; D005334:Fever / Q000134:cerebrospinal fluid / Q000139:chemically induced; D006979:Hyperthermia, Induced; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits
D017304:Annexin A5; D007375:Interleukin-1; D010446:Peptide Fragments; D015232:Dinoprostone