TY - JOUR
T1 - Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non- Hodgkin's lymphoma patients
AU - Singh, Rakesh K.
AU - Varney, Michelle L.
AU - Ino, Kazuhiko
AU - Vose, Julie M.
AU - Bierman, Philip J.
AU - Talmadge, James E.
PY - 2000/5
Y1 - 2000/5
N2 - Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.
AB - Objective. In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. Materials and Methods. We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. Results. Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-γ and tumor necrosis factor-α were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-γ were decreased significantly on day 365 compared with pretransplant levels. Conclusion. The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine. (C) 2000 International Society for Experimental Hematology.
KW - Cytokines
KW - Gene expression
KW - Immune reconstitution
KW - NHL
KW - Stem cell transplantation
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U2 - 10.1016/S0301-472X(00)00145-4
DO - 10.1016/S0301-472X(00)00145-4
M3 - Article
C2 - 10812239
AN - SCOPUS:0034018324
VL - 28
SP - 499
EP - 507
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 5
ER -