Background & Aims: Proper adrenal glucocorticoid secretion is crucial in th
e course of inflammatory diseases. However, the function and structure of t
he adrenal glands have not been examined in inflammatory bower diseases. Me
thods: After induction of trinitrobenzene sulfonic acid (TNBS) colitis in S
JL/J mice, plasma hormone and cytokine levels were measured, adrenal struct
ure was analyzed by immunohistochemistry and electron microscopy, and adren
al cytokine/cytokine receptor expression were studied by RNase protection.
Results: Adrenals of colitic animals were enlarged and hypervascularized. T
hese animals had a marked increase in plasma corticosterone levels during t
he course of colitis (270 +/- 34 vs. 16 +/- 11 ng/mL; P < 0.0001) but only
a modest elevation of their concurrent adrenocorticotropin levels (57 +/- 1
3 vs. 29 +/- 9 pmol/L; NS). On electron microscopy, adrenocortical cells sh
owed ultrastructural signs of marked stimulation, and intra-adrenal lymphoc
ytes were frequently found in direct contact with these cells. Concurrent p
lasma levels of interleukin (IL)-6, the major cytokine activating the hypot
halamic-pituitary-adrenal axis, were markedly increased (495 +/- 131 vs. 20
+/- 1.5 pg/mL; P < 0.0001), and this cytokine directly stimulated corticos
terone secretion by adrenocortical cells in vitro. Intra-adrenal expression
of IL-6 in animals With colitis was increased 80-fold, and the IL-6 recept
or subunits Il-6R alpha and gp130 were present in the adrenal cells. Treatm
ent of animals with neutralizing anti-IL-6 antibody reduced the TNBS-induce
d growth and activation of the adrenal cortices. Conclusions: Colitis is as
sociated with a profound stimulation of adrenocortical cell function and gl
ucocorticoid release. Direct immune-adrenal interactions seem to contribute
to this activation of the adrenal glands during colitis.