• Citer

Adrenal cortical activation in murine colitis.

par Franchimont, Denis ;Bouma, G;Galon, J;Wolkersdörfer, G W;Haidan, A;Chrousos, G P;Bornstein, S R
Référence Gastroenterology, 119, 6, page (1560-1568)
Publication Publié, 2000-12

Article révisé par les pairs

• Détails
• Contenu

Résumé :

BACKGROUND & AIMS: 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.