Decreased interleukin-1 production in aplastic anemia

Interleukin-1 (IL-1), a monocyte factor, plays a central role in the regulation of the immune response; recent data have suggested that IL-1 is the same molecule as hemopoietin-1, a growth factor acting on the multipotent hematopoietic stem cell. IL-1 affects hematopoiesis (1) in vitro, by inducing the release of colony-stimulating factors and regulating early hematopoietic progenitor cells, and (2) in vivo, by stimulating stem cell recovery in irradiated or chemotherapy-treated mice. Several lines of evidence suggest that aplastic anemia may be mediated by cells of the immune system. We address the issue of abnormal IL-1 production in severe aplastic anemia and attempt to correlate normalization of the levels with response to anti-thymocyte globulin (ATG) therapy.

We studied IL-1 production by monocytes from 21 patients with aplastic anemia using a bioassay for IL-1 activity. Fifteen patients were evaluated before ATG therapy. Eight patients were studied before and three months after ATG. In addition, five patients were evaluated only after ATG treatment. One patient did not respond to ATG but did respond to intravenous acyclovir, and was studied before and after acyclovir therapy. Twenty patients with other hematologic disorders requiring transfusions and 30 normal healthy volunteers were also assessed.

IL-1 production was markedly decreased in 75 percent of patients with aplastic anemia when compared with that in normal control subjects (p less than 0.005). Hematologic recovery correlated with normalization of IL-1 production in all but two cases (p less than 0.04).

These observations represent the first evidence of monocyte dysfunction and deficient hematopoietic growth factor production in aplastic anemia. Decreased IL-1 production may have a pathologic role in some cases of aplastic anemia.