Detection of tumor necrosis factor-alpha in bone marrow plasma and peripheral blood plasma from patients with aplastic anemia.

Plasma levels of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in healthy individuals and patients with aplastic anemia (ApAn). IFN-gamma was not detected in normal peripheral blood plasma (PBP) or bone marrow plasma (BMP) and was present in PBP from only 2 of 22 patients and in BMP from 1 of 14 patients and the levels were low (< 1.5 U/ml). Elevated levels of TNF-alpha were present in BMP and PBP from patients but not in control (healthy donor) PBP and BMP. Eleven of twenty-four patients had elevated levels of TNF-alpha in their PBP and 6 of 13 patients had detectable levels of TNF-alpha in their BMP. Only one of the 14 healthy control donors had detectable TNF-alpha and the level was very low (7 pg/ml), while 13 of the 27 ApAn patients had detectable TNF-alpha (P = .009, chi-square test). Not surprisingly, the centers of the distributions of TNF-alpha concentrations of the controls and ApAn patients differed significantly (P < .017 for control and patient PBP and P < .056 for control and patient BMP, Wilcoxon rank-sum test). Spontaneous production of IFN-gamma and TNF-alpha by cultured bone marrow mononuclear cells was observed in four of seven patients but not in the six healthy controls (P = 0.026). Spontaneous production of IFN-gamma and TNF-alpha by cultured peripheral blood mononuclear cells from patients and controls was however similar. Phytohemagglutinin (PHA)-induced production of IFN-gamma and TNF-alpha by cultured mononuclear cells did not differ significantly between ApAn patients and normal controls. The significance of overproduction of TNF-alpha in the pathophysiology of ApAn is discussed.