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Am J Physiol Cell Physiol 279: C2004-C2010, 2000;
0363-6143/00 $5.00
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Vol. 279, Issue 6, C2004-C2010, December 2000

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

Markus W. Knöferl1, Doraid Jarrar2, Martin G. Schwacha2, Martin K. Angele3, William G. Cioffi4, Kirby I. Bland2, and Irshad H. Chaudry2

4 Department of Surgery, Center for Surgical Research, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903; 2 Department of Surgery, School of Medicine, University of Alabama-Birmingham, Birmingham, Alabama 35294; 1 Department of Trauma-Surgery, University of Ulm, 89075 Ulm, Germany; and 3 Department of Surgery, Klinikum Grosshadern, 81377 Munich, Germany

A gender dimorphic immune response has been observed after trauma and severe hemorrhage, a condition believed to be associated with tissue hypoxia. Although studies have shown that hypoxemia per se in males causes a systemic inflammatory response, it is unclear if the inflammatory response to hypoxemia exhibits gender dimorphic characteristics. To study this, male and female C3H/HeN mice in the proestrus state of the estrous cycle were subjected to hypoxemia (95% N2-5% O2) or sham hypoxemia (room air) for 60 min. Later (2 h), plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were determined along with splenic immune responses. Plasma IL-6 and TNF-alpha concentrations after hypoxemia were significantly increased in males but not in females. Splenocyte proliferation was depressed in males after hypoxemia but not in females. A shift toward an immunosuppressive Th-2 cytokine profile was observed in males after hypoxemia [decreased interferon-gamma (Th-1) and increased IL-10 (Th-2)], whereas no such shift was observed in females. Splenic macrophage IL-6, IL-10, and IL-12 production were suppressed in males after hypoxemia; however, such suppression was not observed in females. These findings therefore indicate that a gender dimorphic immune response also exists after hypoxemia in the absence of blood loss and tissue trauma, similar to trauma-hemorrhage. Furthermore, because no systemic inflammatory response or alterations in T lymphocyte or macrophage functions are observed in proestrus females but such parameters are markedly altered after severe hypoxemia in males, these studies indicate that proestrus females can tolerate hypoxemia better than males.

rodent; inflammation; cytokines; sex steroids; proestrus


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