Sublethal hemorrhagic shock reduces tumor necrosis factor-alpha-producing capacity in different cell compartments.
Hemorrhagic shock results in a severe impairment of the immune response. Immunological alterations after hemorrhagic shock thus appear to be responsible for reduced resistance to infectious agents commonly observed after shock and severe injury. In the present study we examined the TNF-alpha-producing capacity of immune cells derived from different organs after sublethal shock in rats. Hemorrhagic shock was established by pressure controlled bleeding to a mean arterial pressure of 35 mm Hg for 35-40 min and consecutive resuscitation in male Sprague-Dawley rats. Twenty four hours after shock, TNF-a production in response to lipopolysaccharide (LPS, Salmonella friedenau) stimulation was measured in isolated spleen, bone marrow and blood cells. TNF-a production could be induced by stimulation with 1 ng/ml, in blood, spleen and bone marrow cells collected from sham-operated animals. A maximal stimulation was observed in all cell types after stimulation with 10 ng/ml LPS and could not be further increased with LPS doses of 100 ng/ml. Hemorrhagic shock of 35 mm Hg for 35-40 min, with consecutive resuscitation did not result in mortality, in contrast to a 4 hours lasting hemorrhagic shock resulting in 80% mortality. Blood, spleen or bone marrow cells, harvested from animals 24 hours after sublethal hemorrhagic shock, showed a significantly reduced TNF-alpha production in all cell populations after LPS stimulation. Serum collected from animals 2 hours after sublethal hemorrhagic shock contained an activity not present either before or 24 hours after shock, that downregulated LPS-induced TNF-alpha production in rat whole blood cultures and the murine macrophage cell line J774. The inhibitory activity present in serum, 2 hours after shock is not IL-10 since this mediator was not detectable in any serum sample. However, in the serum samples with TNF-alpha-inhibitory activity, elevated levels of PGE2 metabolites were found, which suggests the involvement of prostaglandins in trauma-induced immunosuppression. Altered TNF-a expression might be partially explained by an inhibitory activity in the serum already present 2 hours after shock. Since adequate, but not overwhelming TNF-alpha production is essential for host response, the altered cytokine formation might explain local and systemic susceptibility to infections after hemorrhagic shock.
Flohé
S
S
University Hospital Essen, Department of Trauma Surgery, Hufelandstr. 55, 45122 Essen, Germany.
Ackermann
M
M
Reuter
M
M
Nast-Kolb
D
D
Schade
F U
FU
D000818:Animals; D001794:Blood Pressure; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D020896:Hypovolemia; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012475:Salmonella; D012771:Shock, Hemorrhagic / Q000097:blood / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha