Tumor necrosis factor‐α 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 (O 2−) released by activated phagocytes. Recent studies have shown that certain lymphokines such as tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) can significantly enhance O 2− production by phagocytic cells. To ascertain lymphokine production in FA patients, we measured TNF‐α and IFN‐γ production in vivo and in vitro. TNF‐α 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‐α was detected in only one of 25 control (healthy donor) plasma, and the level was very low (7 pg/ml). IFN‐γ levels in normal and patient plasma were negligible. Spontaneous and phytohemagglutinin (PHA)‐induced production of IFN‐γ and TNF‐α by cultured peripheral blood mononuclear cells did not differ significantly between FA patients and normal controls. The significance of overproduction of TNF‐α in vivo in the pathophysiology of FA is discussed. © 1993 Wiley‐Liss, Inc.