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.
Schultz
J C
JC
Department of Pediatrics, University of Wisconsin, Madison.
Shahidi
N T
NT
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma