Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue

Nature. 1988 Aug 25;334(6184):698-700. doi: 10.1038/334698a0.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Analgesia
  • Animals
  • Carrageenan
  • Cyclooxygenase Inhibitors
  • Dinoprostone
  • Hyperalgesia / chemically induced*
  • Hyperesthesia / chemically induced*
  • Indomethacin / pharmacology
  • Interleukin-1 / analogs & derivatives*
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Interleukin-1beta
  • Molecular Sequence Data
  • Nociceptors / physiology*
  • Pain Measurement
  • Peptide Fragments / pharmacology*
  • Prostaglandins / metabolism
  • Prostaglandins E
  • Rats

Substances

  • Cyclooxygenase Inhibitors
  • Interleukin-1
  • Interleukin-1beta
  • Peptide Fragments
  • Prostaglandins
  • Prostaglandins E
  • interleukin 1beta (193-195)
  • Carrageenan
  • Dinoprostone
  • Indomethacin