Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue.
Interleukin-1 (IL-1) describes two inflammatory proteins, IL-1 alpha and IL-1 beta, produced by activated macrophages and other cell types and encoded by two genes. Their amino acid sequences have only 26% similarity, but their biological activities are comparable, with a few exceptions; indeed, both molecules appear to act at the same receptor. As IL-1 release prostaglandins which sensitize nociceptors in man and in experimental animals, we tested IL-1 alpha and IL-1 beta in rats for hyperalgesic (nociceptive) activity. Our results show that IL-1 beta given systemically is an extremely potent hyperalgesic agent with a probable peripheral site of action; IL-1 alpha is approximately 3,000 times less active than IL-1 beta. We have delineated the region of IL-1 beta mediating the hyperalgesic effect and developed an analgesic tripeptide analogue of IL-1 beta which antagonizes hyperalgesia evoked by IL-1 beta and by the inflammatory agent carrageenan.
D000595:Amino Acid Sequence; D000698:Analgesia; D000818:Animals; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006930:Hyperalgesia / Q000139:chemically induced*; D006941:Hyperesthesia / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D053583:Interleukin-1beta; D008969:Molecular Sequence Data; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011458:Prostaglandins E; D051381:Rats
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D011453:Prostaglandins; D011458:Prostaglandins E; C056932:interleukin 1beta (193-195); D002351:Carrageenan; D015232:Dinoprostone; D007213:Indomethacin