IL-6 and IL-8 levels in plasma during hematopoietic progenitor transplantation

Abstract

BACKGROUND AND OBJECTIVE: The relationship between cytokine concentrations and transplant-related complications has been studied in bone marrow transplant patients. The changes in TNF-alpha, IL-1 and IL-6 concentrations after transplantation are well documented in the literature but this is not the case for IL-8. The purpose of the present study was to investigate prospectively the plasma concentration of these cytokines and their relationship to transplant-related complications. DESIGN AND METHODS: Pro-inflammatory cytokine (TNF-alpha, IL-1, IL-6 and IL-8) levels in plasma were determined in a group of 53 patients undergoing hematopoietic progenitor transplantation. Plasma samples were collected weekly from day -7 to day +35 and stored at -70 degrees C until assayed by ELISA. The major transplant-related toxicities registered were: veno-occlusive disease (VOD), acute graft-versus-host disease (GVHD), infectious episodes, renal failure and mucositis. RESULTS: In spite of the great variability of plasma cytokine profiles between the different patients, we came to various conclusions. Patients' TNF-alpha and IL-1 concentrations correlated well over time. IL-6 and IL-8 profiles were similar and correlated well with febrile episodes. In some cases, an increase in IL-6 preceded hematologic recovery. In our study, increased levels of TNF-alpha, IL-6 and especially IL-8 correlated with hepatic or renal dysfunction as evaluated by increased bilirubin and creatinine in plasma, while pulmonary complications correlated only with increased IL-6 levels. Allogeneic transplant patients had a tendency to have higher TNF-alpha concentrations than autologous transplant patients, probably because an allogeneic transplant is associated with more transplant-related toxicity. Basal disease usually had no effect on cytokine profiles. INTERPRETATION AND CONCLUSIONS: IL-6 and IL-8 were the only cytokines studied whose increase correlated with febrile episodes. High IL-8 values may be a useful predictor of renal dysfunction and pulmonary disease and seems to trigger off high IL-6 levels. Plasma TNF-alpha and IL-1 concentrations during the posttransplant period have not been shown to be predictive of the development of transplant-related complications, and none of the profiles was recognized to be specific for a particular complication in this study.