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 chemotherapy and peripheral stem cell transplantation.


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.
Singh
R K
RK
Department of Pathology and Microbiology, and, University of Nebraska Medical Center, Omaha, Nebraska, USA. rsingh@unmc.edu
Varney
M L
ML
Ino
K
K
Vose
J M
JM
Bierman
P J
PJ
Talmadge
J E
JE
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D016207:Cytokines / Q000235:genetics*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014158:Transcription, Genetic; D014182:Transplantation, Autologous / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor