Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF

Am J Physiol. 1999 Apr;276(4):G1027-36. doi: 10.1152/ajpgi.1999.276.4.G1027.


We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day 1 and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cerebral Ventricles / drug effects*
  • Cerebral Ventricles / physiology
  • Cerebral Ventricles / physiopathology
  • Colitis / genetics*
  • Colitis / physiopathology
  • Colitis / psychology*
  • Colon / pathology
  • Corticosterone / blood
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / pharmacology*
  • Corticotropin-Releasing Hormone / physiology*
  • Female
  • Genetic Predisposition to Disease
  • Injections, Intraventricular
  • Intestinal Mucosa / pathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peroxidase / analysis
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Species Specificity
  • Stress, Psychological*
  • Trinitrobenzenesulfonic Acid


  • Neuroprotective Agents
  • Peptide Fragments
  • astressin
  • Trinitrobenzenesulfonic Acid
  • Corticotropin-Releasing Hormone
  • Peroxidase
  • Corticosterone