Endocrine Involvement in Minor (Non-H-2) Graft Versus Host Reaction in Mice: Dissociated Effect on Corticosterone and Aldosterone Plasma Levels

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Abstract
The graft vs. host reaction (GVHR) induced across a non-H-2 histocompatibility antigen barrier was shown to be a multiorgan disease with a strict time-dependent pattern of functional alterations. The present study was undertaken to examine the effects of the GVHR on corticosterone, aldoserone, corticotropin (ACTH), Na+, and K+ plasma concentrations in mice. GVHR was induced in irradiated (DBA/2 .times. B10.D2)F1 mice by transplantation of B10.D2 hemopoietic cells. Controls were untreated F1 mice and irradiated syngeneic (F1) cell-grafted F1 mice. Nonimmunological stimuli transiently increased ACTH and corticosterone plasma levels during the first 5 days, although the early ACTH peak was markedly reduced in GVHR mice. Circulating corticosterone levels returned to normal values thereafter in controls. ACTH returned to basal levels in all mice, even in GVHR mice in spite of their persistent high corticosteronism. The enhancing effect of GVHR on plasma aldosterone concentrations was delayed until day 30 after the cell graft. Results suggest 1) a dissociated effect of GVHR on mineralocorticoid and glucocorticoid metabolism and 2) either an alteration of adrenal sensitivity to ACTH in GVHR mice or a possible mimicking of some neuroendocrine activities by the lymphocyes responsible for the onset of the disease.