Detection of tumor necrosis factor‐α in bone marrow plasma and peripheral blood plasma from patients with aplastic anemia

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Abstract
Plasma levels of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were determined in healthy individuals and patients with aplastic anemia (ApAn). IFN-γ 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-α 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-α in their PBP and 6 of 13 patients had detectable levels of TNF-α in their BMP. Only one of the 14 healthy control donors had detectable TNF-α and the level was very low (7 pg/ml), while 13 of the 27 ApAn patients had detectable TNF-α (P = .009, chi-square test). Not surprisingly, the centers of the distributions of TNF-α 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-γ and TNF-α 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-γ and TNF-α by cultured peripheral blood mononuclear cells from patients and controls was however similar. Phytohemagglutinin (PHA)-induced production of IFN-γ and TNF-α by cultured mononuclear cells did not differ significantly between ApAn patients and normal controls. The significance of overproduction of TNF-α in the pathophysiology of ApAn is discussed.

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