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-gamma and tumor necrosis factor-alpha 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-gamma were decreased significantly on day 365 compared with pretransplant levels. CONCLUSIONS: 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.
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 lymphomapatients 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-gamma and tumor necrosis factor-alpha 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-gamma were decreased significantly on day 365 compared with pretransplant levels. CONCLUSIONS: 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.
Authors: Kevin Hendrawan; Melissa L M Khoo; Malini Visweswaran; Jennifer C Massey; Barbara Withers; Ian Sutton; David D F Ma; John J Moore Journal: Front Immunol Date: 2022-01-19 Impact factor: 7.561