Anemia of inflammation: role of T lymphocyte activating factor.

Abstract

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.