Differential production of prostaglandin E2 in male and female mice subjected to thermal injury contributes to the gender difference in immune function:: Possible role for 15-hydroxyprostaglandin dehydrogenase

We have previously reported a macrophage-mediated gender difference in postburn immunosuppression, which was dependent upon elevated levels of circulating 17 beta -estradiol (E-2) and, in part, interleukin-6. Herein we examined the role of prostaglandin E-2 (PGE(2)), a potent suppressor of cell-mediated immunity, Circulating levels of PGE(2) were significantly elevated in females but not males at 10 days postburn (P < 0.01), and indomethacin treatment fully restored the delayed-type hypersensitivity and splenocyte proliferative responses of thermally injured females. While there was no difference in cyclooxygenase-a protein expression in the lungs and liver of thermally injured male and female mice, there was a marked decrease in the protein expression of 15-hydroxyprostaglandin dehydrogenase in females. These data demonstrate that PGE(2) is a critical mediator of immunosuppression in thermally injured female mice and that the increase in circulating PGE(2) is derived, in part, from decreased degradation and clearance of PGE(2). (C) 2000 Academic Press.