Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys

J Storek, T Gillespy III, H Lu, A Joseph… - Blood, The Journal …, 2003 - ashpublications.org
J Storek, T Gillespy III, H Lu, A Joseph, MA Dawson, M Gough, J Morris, RC Hackman…
Blood, The Journal of the American Society of Hematology, 2003ashpublications.org
Abstract 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 μg/kg twice a day subcutaneously)
between 6 and 10 weeks after transplantation. The mean increase in blood absolute CD4 T …
Abstract
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 μg/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.
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