BONE-MARROW FIBROBLASTS FROM CHILDREN WITH APLASTIC-ANEMIA EXHIBIT REDUCED INTERLEUKIN-6 PRODUCTION IN RESPONSE TO CYTOKINES AND VIRAL CHALLENGE

Defects of the bone marrow microenvironment have been implicated in th e pathogenesis of aplastic anemia (AA). We examined granulocyte/macrop hage colony-stimulating factor (GM-CSF) and IL-6 production in bone ma rrow fibroblasts from five children with AA in response to cytokines a nd viral challenge with cytomegalovirus (CMV). Cytokine-stimulated IL- S production in patients' fibroblasts was significantly reduced, where as GM-CSF production was found to be comparable to normal controls. Al so, CMV-mediated stimulation of IL-6 production was significantly lowe r in bone marrow fibroblasts from patients with AA. During the late ph ase of CMV-infection, IL-6 production was suppressed in CMV-infected f ibroblasts from patients with AA with 90% inhibition of IL-6 protein p roduction and marked reduction in IL-6 mRNA accumulation. Defective IL -6 production in bone marrow fibroblasts might contribute to hematopoi etic suppression in some patients with AA.