Interleukin-6 (IL-6) levels in febrile children during maximal aplasia after bone marrow transplantation (BMT) are similar to those in children with normal hematopoiesis

Abstract

Interleukin-6 (IL-6) has been shown to be an inducer of the acute-phase response (APR) and to be involved in the pathogenesis of several disease states, including graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (BMT). As blood cells of the monocyte lineage are known to be major producers of this cytokine, we wondered whether extreme peripheral leukopenia following total ablation of hematopoiesis could compromise IL-6 production during the first days after allogeneic or autologous BMT. In the absence of detectable circulating leukocytes we measured elevated IL-6 levels in six children having fever (≥38° C) of presumed infectious origin with an average of 74±60 units/ml (range 19–309 units/ml). IL-6 levels in febrile children having a normal hematopoiesis (118±254 units/ml, range 17–1213 units/ml) were not significantly higher than those found in the febrile BMT group (p>0.05). Moreover, there was a clear association between elevated IL-6 levels and the presence of fever. C-reactive protein (CRP) was also elevated (≥1 mg/dl), whereas tumor-necrosis factor alpha (TNF) was undetectable (<1 pg/ml). Two transplanted patients without fever during the period of total aplasia had neither detectable CRP nor IL-6, thus demonstrating that the transplant procedure itself does not induce an APR. Our data obtained during maximal leukopenia following BMT show that a functional hematopoietic system is not necessary for regular production of IL-6, which is associated with fever. Cells of nonhematopoietic origin may contribute to this production.