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 17β-estradiol (E2) and, in part, interleukin-6. Herein we examined the role of prostaglandin E2 (PGE2), a potent suppressor of cell-mediated immunity. Circulating levels of PGE2 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-2 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 PGE2 is a critical mediator of immunosuppression in thermally injured female mice and that the increase in circulating PGE2 is derived, in part, from decreased degradation and clearance of PGE2.