ENDOGENOUS INTERLEUKIN-1 RECEPTOR ANTAGONIST DURING HUMAN BONE-MARROWTRANSPLANTATION - INCREASED LEVELS DURING GRAFT-VERSUS-HOST DISEASE, DURING INFECTIOUS COMPLICATIONS, AND AFTER IMMUNOGLOBULIN THERAPY

In order to understand in more detail the role of endogenous interleuk in 1 receptor antagonist (IL-1ra) during bone marrow transplantation, IL-1ra serum levels of 28 patients undergoing allogeneic (n=25) or aut ologous (n=3) bone marrow transplantation were measured with a commerc ially available ELISA. In addition, the impact of intravenous immunogl obulin (IVIG) was evaluated by analyzing IL-1ra serum levels before an d 2, 5, and 24 hr after IVIG infusion. IL-1ra measurements revealed a nadir of circulating IL-1ra levels 3-5 days after bone marrow transpla ntation, with an increase during conditioning and hematological recons titution. Circulating IL-1ra levels were significantly increased in pa tients with cytomegalovirus (CMV) disease, CMV reactivation, graft-ver sus-host disease (GVHD), or fever of unknown origin, when compared wit h time-matched controls without complications. Highest levels were obs erved in patients with CMV disease (1922+/-388 pg/ml), followed by pat ients with CMV reactivation (1575+/-435 pg/ml) and GVHD (1178+/-317 pg /ml). The magnitude of IL-1ra increase in GVHD was related to disease severity. Patients with grade III-IV GVHD developed higher IL-1ra leve ls than did patients with grade I-II GVHD. Lower but still significant ly elevated IL-1ra levels were observed during fever of unknown origin (384+/-87 pg/ml). An increase of IL-1ra serum levels followed the adm inistration of IVIG before transplantation and after hematopoietic rec onstitution, but not during aplasia, pointing to the important role of hematopoietic cells in the production of IL-1ra. In conclusion, we sh ow that IL-1ra release is related to conditioning regimen, hematopoiet ic reconstitution, complications of infectious and alloimmune etiology after bone marrow transplantation, and exogenously administered IVIG.