Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys.
In mice, interleukin-7 (IL-7) hastens T-cell reconstitution and might cause autoimmune diseases, lymphoma, and osteoporosis. We assessed the effect of IL-7 on T-cell reconstitution and toxicity in baboons that underwent total body irradiation followed by autologous transplantation of marrow CD34 cells. Three baboons received placebo and 3 baboons received recombinant human IL-7 (rhIL-7, 75 microg/kg twice a day subcutaneously) between 6 and 10 weeks after transplantation. The mean increase in blood absolute CD4 T-cell counts was 0.9-fold in the placebo-treated animals versus 9.0-fold in those treated with IL-7 (P =.02). The increase observed in the IL-7-treated animals appeared attributable to peripheral expansion rather than de novo generation. The IL-7-treated animals had greater mean increases in the volumes of the spleen (2.0-fold with placebo versus 4.5-fold with IL-7, P =.02) and lymph nodes (1.8-fold with placebo versus 4.1-fold with IL-7, P =.10) but not the thymus (3.4-fold with placebo versus 1.1-fold with IL-7, P =.18). Side effects of IL-7 included thrombocytopenia and possibly neutropenia and hemolytic anemia. One IL-7-treated animal failed to thrive due to a disease resembling graft-versus-host disease. No animals developed lymphoma. Bone density was not decreased. In conclusion, IL-7 raises CD4 T-cell counts in irradiated primates. It remains to be determined whether this is associated with clinical benefit.
Storek
Jan
J
Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jstorek@fhcrc.org
Gillespy
Thurman
T
Lu
Hailing
H
Joseph
Ansamma
A
Dawson
Monja A
MA
Gough
Michael
M
Morris
Julia
J
Hackman
Robert C
RC
Horn
Peter A
PA
Sale
George E
GE
Andrews
Robert G
RG
Maloney
David G
DG
Kiem
Hans-Peter
HP
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017931:DNA Primers; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology / Q000627:therapeutic use*; D008285:Major Histocompatibility Complex; D010215:Papio; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins; D019089:Stem Cell Factor / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous / Q000276:immunology*
D018952:Antigens, CD34; D017931:DNA Primers; D015851:Interleukin-7; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim