Severe hypoxemia in the absence of blood loss causes a gender dimorphic immune response

A gender dimorphic immune response has been observed after trauma and sever e hemorrhage, a condition believed to be associated with tissue hypoxia. Al though studies have shown that hypoxemia per se in males causes a systemic inflammatory response, it is unclear if the inflammatory response to hypoxe mia exhibits gender dimorphic characteristics. To study this, male and fema le C3H/HeN mice in the proestrus state of the estrous cycle were subjected to hypoxemia (95% N-2-5% O-2) or sham hypoxemia (room air) for 60 min. Late r (2 h), plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha le vels were determined along with splenic immune responses. Plasma IL-6 and T NF-alpha concentrations after hypoxemia were significantly increased in mal es but not in females. Splenocyte proliferation was depressed in males afte r hypoxemia but not in females. A shift toward an immunosuppressive Th-2 cy tokine profile was observed in males after hypoxemia [decreased interferon- gamma (Th-1) and increased IL-10 (Th-2)], whereas no such shift was observe d in females. Splenic macrophage IL-6, IL-10, and IL-12 production were sup pressed in males after hypoxemia; however, such suppression was not observe d in females. These findings therefore indicate that a gender dimorphic imm une response also exists after hypoxemia in the absence of blood loss and t issue trauma, similar to trauma-hemorrhage. Furthermore, because no systemi c inflammatory response or alterations in T lymphocyte or macrophage functi ons are observed in proestrus females but such parameters are markedly alte red after severe hypoxemia in males, these studies indicate that proestrus females can tolerate hypoxemia better than males.