Dehydroepiandrosterone restores immune function following trauma-haemorrhage by a direct effect on T lymphocytes

Although a profound depression in immune function occurs following injury, the mechanism responsible for this is not fully understood. Furthermore, st eroid hormones are known to be important mediators in the regulation of imm une function, Although dehydroepiandrosterone (DHEA), the most plentiful st eroid hormone, has been shown to stimulate immune function in normal animal s, it is unknown whether DHEA has any salutary or detrimental effects on im mune responses after trauma and haemorrhage, To study this, male mice were subjected to trauma, haemorrhage and resuscitation, following which they re ceived either DHEA or vehicle subcutaneously. DHEA administration restored the normally depressed splenocyte proliferation as well as interleukin 2, i nterleukin 3, and interferon gamma elaboration following trauma and haemorr hage, In an attempt to determine the mechanisms mediating this effect, T ce lls were stimulated in vitro in the presence of DHEA and a variety of hormo ne antagonists. The stimulatory effect of DHEA on splenocyte proliferation was unaltered by the testosterone receptor antagonist flutamide, while the oestrogen antagonist tamoxifen completely abrogated its effect. In addition , DHEA administration normalized the elevated serum corticosterone level ty pically seen following injury, These results indicate, therefore, that DHEA improves splenocyte function after trauma and haemorrhage by directly stim ulating T cells and also by preventing a rise in serum cortisosterone. (C) 1999 Academic Press.