Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non-Hodgkin's lymphoma patients

Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chem otherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels an d the immune phenotype and function in the peripheral blood mononuclear cel ls from intermediate-grade non-Hodgkin's lymphoma patients prior to and fol lowing high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokin es and monokines were observed in patients undergoing high-dose chemotherap y and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, inter feron-gamma and tumor necrosis factor-alpha were significantly higher than in normal individuals, In addition, on days 30 and 100 following transplant ation interleukin-10 levels were significantly increased compared with pret reatment levels. In contrast, the levels of interleukin-2 mRNA and interfer on-gamma were decreased significantly on day 365 compared with pretransplan t levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increas ed cellular frequency; rather, they appear to be due to abnormal cellular a ctivation, However, T-cell function is significantly depressed compared wit h normal donors, which is associated with significantly higher levels of ce llular-dependent T cell inhibitory activity and, we suggest herein, high le vels of interleukin-10, a type 2 cytokine, (C) 2000 International Society f or Experimental Hematology, Published by Elsevier Science Inc.