Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

Am J Physiol. 1998 Nov;275(5):E757-62. doi: 10.1152/ajpendo.1998.275.5.E757.

Abstract

Urocortin (UCN) is a neuropeptide homologous with corticotropin-releasing factor (CRF), which has anti-inflammatory activities not all mediated by corticosteroids. In mice, UCN (1 microg/mouse sc) significantly reduced lipopolysaccharide (LPS)-induced serum tumor necrosis factor (TNF) and interleukin (IL)-1beta levels in vivo but did not affect serum IL-6. These effects were paralleled by a rise in corticosterone (CS) levels. Blockade of the CS increase by cyanoketone did not prevent TNF inhibition by UCN, suggesting the neuropeptide has anti-inflammatory mechanisms independent of the hypothalamus-pituitary-adrenal axis. In fact UCN had a direct inhibitory effect on LPS-induced TNF in rat Kupffer cells at concentrations between 10(-10) and 10(-16) M, and this effect was related to increased cAMP levels. However, the in vivo inhibition of LPS-induced IL-1beta by UCN was reversed by cyanoketone, indicating that the increase of endogenous glucocorticoids might be more important in IL-1beta inhibition than in TNF inhibition by UCN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / pharmacology*
  • Animals
  • Cells, Cultured
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / pharmacology*
  • Corticotropin-Releasing Hormone / physiology
  • Cyanoketone / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology
  • Kinetics
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Rats
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Urocortins

Substances

  • Adrenal Cortex Hormones
  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Urocortins
  • Cyanoketone
  • Corticotropin-Releasing Hormone