Decreased IL-1 beta and TNF alpha secretion in long-term bone marrow culture supernatant from Fanconi's anaemia patients.
Recent studies have shown that abnormalities of cytokine and lymphokine secretion are involved in the pathophysiology of Fanconi's anaemia (FA). In the present study, we quantified IL-1 beta, IL-1 receptor antagonist (IL-1Ra), IL-6 and TNF alpha protein levels in the supernatant of long-term cultures generated from BM cells of FA patients. Cell-free conditioned medium from long-term bone marrow culture was harvested every week at confluence and tested for interleukin secretion. IL-1 beta, IL-1Ra, TNF alpha and IL-6 protein secretion was assessed using immunoassays. IL-6 secretion was similar between controls and FA supernatants from wk 1 to wk 4. TNF alpha released from FA cells was consistently found at very low levels compared to control cells during the first 3 wk. Furthermore, secretion of IL-1 beta by cells from FA was always more than 2 standard deviations below the value of IL-1 beta found in normal donor cells from wk 1 to wk 4. In conclusion, in addition to a stem cell defect, a marked decrease in IL-1 beta and TNF alpha secretion may be one of the mechanisms leading to bone marrow failure in individuals with Fanconi's anaemia.
Pharmacology Laboratory, Saint-Louis Hospital, Paris, France.
P
P
de Cremoux
E
E
Gluckman
M P
MP
Podgorniak
C
C
Menier
D
D
Thierry
F
F
Calvo
G
G
Socié
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D005199:Fanconi Anemia / Q000473:pathology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha