Tumor necrosis factor-alpha overproduction in Fanconi's anemia

Various in vitro studies and clinical observations suggest that Fanconi's anemia (FA) patients are unable to detoxify adequately superoxide anions (O2-) released by activated phagocytes. Recent studies have shown that certain lymphokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) can significantly enhance O2- production by phagocytic cells. To ascertain lymphokine production in FA patients, we measured TNF-alpha and IFN-gamma production in vivo and in vitro. TNF-alpha was detected in the plasma of 16 of 18 FA patients with concentrations ranging from 6 to 131 pg/ml (mean 31 pg/ml). TNF-alpha was detected in only one of 25 control (healthy donor) plasma, and the level was very low (7 pg/ml). IFN-gamma levels in normal and patient plasma were negligible. Spontaneous and phytohemagglutinin (PHA)-induced production of IFN-gamma and TNF-alpha by cultured peripheral blood mononuclear cells did not differ significantly between FA patients and normal controls. The significance of overproduction of TNF-alpha in vivo in the pathophysiology of FA is discussed.