title: Adrenal cortical activation in murine colitis.
abstract: OBJECTIVE
  Proper adrenal glucocorticoid secretion is crucial in the course of inflammatory diseases. However, the function and structure of the adrenal glands have not been examined in inflammatory bowel diseases.
  
  
  METHODS
  After induction of trinitrobenzene sulfonic acid (TNBS) colitis in SJL/J mice, plasma hormone and cytokine levels were measured, adrenal structure was analyzed by immunohistochemistry and electron microscopy, and adrenal cytokine/cytokine receptor expression were studied by RNase protection.
  
  
  RESULTS
  Adrenals of colitic animals were enlarged and hypervascularized. These animals had a marked increase in plasma corticosterone levels during the course of colitis (270 +/- 34 vs. 16 +/- 11 ng/mL; P < 0.0001) but only a modest elevation of their concurrent adrenocorticotropin levels (57 +/- 13 vs. 29 +/- 9 pmol/L; NS). On electron microscopy, adrenocortical cells showed ultrastructural signs of marked stimulation, and intra-adrenal lymphocytes were frequently found in direct contact with these cells. Concurrent plasma levels of interleukin (IL)-6, the major cytokine activating the hypothalamic-pituitary-adrenal axis, were markedly increased (495 +/- 131 vs. 20 +/- 1.5 pg/mL; P < 0.0001), and this cytokine directly stimulated corticosterone secretion by adrenocortical cells in vitro. Intra-adrenal expression of IL-6 in animals with colitis was increased 80-fold, and the IL-6 receptor subunits IL-6R alpha and gp130 were present in the adrenal cells. Treatment of animals with neutralizing anti-IL-6 antibody reduced the TNBS-induced growth and activation of the adrenal cortices.
  
  
  CONCLUSIONS
  Colitis is associated with a profound stimulation of adrenocortical cell function and glucocorticoid release. Direct immune-adrenal interactions seem to contribute to this activation of the adrenal glands during colitis.
authors: Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: D
authors: D
authors: Franchimont
authors: G
authors: G
authors: Bouma
authors: J
authors: J
authors: Galon
authors: G W
authors: GW
authors: Wolkersdörfer
authors: A
authors: A
authors: Haidan
authors: G P
authors: GP
authors: Chrousos
authors: S R
authors: SR
authors: Bornstein
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003345:Corticosterone / Q000378:metabolism; D004198:Disease Susceptibility; D004351:Drug Resistance; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D014302:Trinitrobenzenesulfonic Acid; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D014302:Trinitrobenzenesulfonic Acid; D003345:Corticosterone