Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock

Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide.