Dexamethasone depresses the expression of l-selectin but not the in vivo migration of bovine neutrophils into the uterus

Abstract

There are several indications that periparturient depression of functional properties of polymorphonuclear neutrophilic granulocytes (PMN) may be of great importance for the pathogenesis of genital infections after calving. As the periparturient period is characterized by high plasma levels of corticosteroids, the hypothesis to be tested was that high concentrations of glucocorticoids during the periparturient period suppress uterine PMN in number and functionality. An in vivo endometritis model was applied to examine uterine PMN. Recombinant human interleukin-8 (rhIL-8) was infused into the uterus of estrous cows and heifers 24 h after pretreatment with dexamethasone (0.07 mg/kg i.m.). Six hours after rhIL-8 infusion high numbers of uterine PMN were isolated and characterized as to their immunophenotype and function. Animals treated with dexamethasone animals showed leucocytosis due to neutrophilia in peripheral blood. Despite a downregulation of expressed l-selectin, cattle treated with dexamethasone showed more uterine PMN than those treated with placebo. Dexamethasone decreased plasma concentrations of the immunomodulatory steroidal hormones cortisol and estrogen. Dexamethasone directly reduced the generation of reactive oxygen species (ROS) by uterine PMN. This may be a useful mechanism since it would protect the endometrium from tissue damage by excessive extracellular ROS. However, it is not known if the net effect is in fact a reduction in ROS, as the number of uterine cells increases. Our study shows that glucocorticoids may not be considered immunosuppressive in all cases and may play an important role in the regulation of post partum uterine defense mechanisms.