CHEMICALLY-INDUCED HYPOTENSION INCREASES PGE(2) RELEASE AND DEPRESSESMACROPHAGE ANTIGEN PRESENTATION

Hemorrhagic shock causes severe depression of macrophage-functions and is associated with increased susceptibility to sepsis. Because hemorr hagic shock and resuscitation encompasses several pathophysiological c onditions, such as hypotension, low-flow conditions, hypoxia, and repe rfusion injury, it remains unknown whether severe hypotension in the a bsence of blood loss has any adverse effects on macrophage functions. To study this, systemic arterial hypotension was induced in C3H/HeN mi ce for 15 min by intravenous infusion of sodium nitroprusside or ATP-M gCl2. Peritoneal macrophages (PM) were harvested 20 h later with lavag e. Antigen presentation was measured by coculturing PM with the D10.G4 .1 T(h) cell clone. Tumor necrosis factor (TNF), interleukin (IL)-6, I L-1, and prostaglandin (PG) E2 levels in supernatants of PM stimulated with lipopolysaccharide were measured with bioassays or radioimmunoas say. Systemic arterial hypotension resulted in a significant decrease of PM capacity to present antigen. Although the release of TNF, IL-6, and IL-1 by PM was unaltered after hypotension, PGE2 release by PM was significantly elevated compared with the control group. These data in dicate that chemically induced systemic arterial hypotension without b lood loss leads to a depression of antigen presentation, which may be caused by elevated release of the immunosuppressive eicosanoid PGE2.