Sex differences and estrogen modulation of the cellular immune response after injury

Abstract

Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.

Figure 1

Schematic of events following injury, with the circles representing innate (filled) and adaptive (open) immune responses. SIRS = systemic inflammatory response syndrome; CARS = compensatory anti-inflammatory response syndrome; MODS = multiple organ dysfunction syndrome; MOF = multiple organ failure.