Administration of human recombinant IL-7 to normal and irradiated mice increases the numbers of lymphocytes and some immature cells of the myeloid lineage.
In vitro experiments performed by several investigators have demonstrated that IL-7 is a growth factor for immature B lymphocytes, thymocytes, and mature T lymphocytes. To evaluate the potential therapeutic use for human rIL-7 (rhuIL-7) as a hematopoietin, we have studied the in vivo hematopoietic effects of rhuIL-7 in mice. In these experiments, sublethally irradiated and normal mice were treated with or without rhuIL-7 for up to 26 days. Administration of rhuIL-7 significantly increased the white blood cell count in the peripheral blood and spleen in both normal and irradiated mice. Treatment with rhuIL-7 also accelerated lymphocytic recovery in irradiated mice. Precursor and mature B lymphocytes showed the greatest expansion in response to rhuIL-7 administration, with smaller increases in T lymphocytes being observed. In mice recovering from high dose irradiation, rhuIL-7 treatment resulted in preferential expansion of CD8+ T lymphocytes and more rapid normalization of the CD4/CD8 ratios. Differential analysis of peripheral blood smears demonstrated that rhuIL-7 also increased the numbers of immature granulocytes in both normal and irradiated mice. Moreover, administration of rhuIL-7 to normal, irradiated, cyclophosphamide-pretreated, or 5-fluorouracil-pretreated mice increased the number of acetylcholinesterase-positive megakaryocytes in the spleen, but not the bone marrow. Therefore, although the major in vivo effects of rhuIL-7 were on cells of the lymphocytic lineage, rhuIL-7 also increased the numbers of some immature cells of the myeloid lineage.
Faltynek
C R
CR
Department of Immunopharmacology, Sterling Winthrop Pharmaceuticals Research Division, Malvern, PA 19355.
Wang
S
S
Miller
D
D
Young
E
E
Tiberio
L
L
Kross
K
K
Kelley
M
M
Kloszewski
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000166:cytology; D014916:Whole-Body Irradiation
D015851:Interleukin-7; D011994:Recombinant Proteins; D003520:Cyclophosphamide; D005472:Fluorouracil