Anemia of inflammation: role of T lymphocyte activating factor.
Varied conditions associated with immune activation (rheumatic, infectious and malignant) are associated with a syndrome characterized by selective erythropoietic suppression. The pathogenesis of this anemia is unknown. We have cultured intact marrows from 11 patients and found decreased erythroid colony forming activity (CFU-E: colony forming unit-erythroid; p < 0.01). We analyzed sera from 23 patients with infectious, rheumatic and malignant disorders for their ability to render normal human T lymphocytes inhibitory to autologous CFU-E and burst forming unit-erythroid in vitro. Following exposure to serum from some anemic patients, normal T cells were observed to inhibit autologous CFU-E when compared to the effect elicited by T cells incubated with heterologous normal serum. Pooled data from 19 (7 not anemic, 12 anemic) serum samples using 8 different normal T cell and marrow donors revealed a significant correlation (r = 0.65, p < 0.01) between each patient's hemoglobin level and the ability of his/her serum to render T cells suppressive to CFU-E in vitro. The suppression mediated by patient serum exposed T cells on autologous CFU-E could be ameliorated by increased concentrations of erythropoietin. The serum factor was heat stable (56 degrees C) and could not be eliminated by neutralizing antibody to either gamma-interferon or tumor necrosis factor-alpha. We conclude that some patients with anemia of inflammation may have a circulating factor(s) which renders normal T lymphocytes suppressive to autologous CFU-E in vitro. The presence of a circulating serum factor in these patients may help explain how inflammatory events distant from the marrow mediate the erythropoietic suppression characteristic of this syndrome.
Pixley
J S
JS
Dept. of Medicine University of Nevada School of Medicine, VA Medical Center, Reno 89520.
MacKintosh
F R
FR
Smith
E A
EA
Zanjani
E D
ED
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000503:physiopathology*; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000032:analysis; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D007375:Interleukin-1 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology
D006454:Hemoglobins; D007375:Interleukin-1; D004921:Erythropoietin