ABSTRACT
INTRODUCTION: Mononuclear cells (MNC) from patients with aplastic anemia (AA) can inhibit hematopoietic colony formation from normal bone marrow (BM) cells. Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are considered as soluble mediators of BM suppression in AA. Because of its cytokine synthesis inhibiting action, interleukin-10 (IL-10) could be a potentially useful molecule to modulate the hematopoietic effects of MNC from patients with AA. METHODS: Using coculture experiments we studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro hematopoietic suppression by peripheral blood (PB) MNC from AA patients. RESULTS: PBMNC (5 x 10(5)/ml) from seven patients with AA caused a 40-100% reduction of normal burst-forming unit-erythroid (BFU-E) growth and a 38-91% reduction of colony-forming unit-granulocyte/macrophage (CFU-GM) growth, respectively, in semisolid cocultures. IL-10 was highly effective in reversing growth inhibition in these cocultures. Addition of 10 ng/ml IL-10 to cocultures significantly restored growth of BFU-E in all seven cases and growth of CFU-GM in five of seven cases, respectively. The effect was dose dependent and correlated with decreased IFN-gamma and TNF-alpha production in suspension cultures. Using intracellular cytokine staining it was found that increased TNF-alpha production in AA cells was derived from both CD4+ and CD8+ cells, whereas aberrant IFN-gamma synthesis was only detected in CD8+ cells. CONCLUSION: IL-10 is effective in reversing in vitro hematopoietic suppression by PBMNC from AA patients. These results suggest therapeutic evaluation of rhIL-10 in patients with AA.
