The in vivo effects of recombinant human interleukin-3: demonstration of basophil differentiation factor, histamine-producing activity, and priming of GM-CSF-responsive progenitors in nonhuman primates.
Recently human interleukin-3 (IL-3) produced by molecular cloning was characterized as a growth factor for basophils and eosinophils in human bone marrow cultures. Since we found a similar activity of the human factor on simian bone marrow cells, we investigated the in vivo effects of recombinant human (rh) IL-3 in healthy rhesus monkeys (n = 10). rh IL-3 was administered subcutaneously (SC) to monkeys at different doses (11, 33, and 100 micrograms/kg/d) for 14 days followed by subsequent rh GM-CSF administration (5.5 micrograms/kg/d SC) for another two weeks. During the second week of rh IL-3 administration monkeys responded with a twofold to threefold increase of WBCs caused by a dose-dependent elevation of basophils (up to 40% of WBCs) and eosinophils. rh IL-3 also induced a dose-dependent increase of histamine (up to 700-fold above normal values) in monkey blood cells. Administration of rh GM-CSF to rh IL-3 pretreated monkeys resulted in a twofold enhanced increase in WBCs (due mainly to eosinophils and neutrophils) compared with animals treated with rh GM-CSF alone. Simultaneous administration of both cytokines (100 micrograms/kg rh IL-3 + 5.5 micrograms/kg rh GM-CSF SC) to two separate monkeys for 14 days induced a WBC elevation similar to that observed in monkeys treated with rh GM-CSF alone. In conclusion, our results indicate that rh IL-3 is a differentiation factor for blood basophils and primes the hematopoietic system for subsequent rh GM-CSF actions.
Mayer
P
P
Sandoz Research Center, Vienna, Austria.
Valent
P
P
Schmidt
G
G
Liehl
E
E
Bettelheim
P
P
D000818:Animals; D001491:Basophils / Q000378:metabolism / Q000502:physiology*; D001853:Bone Marrow / Q000502:physiology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006632:Histamine / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007377:Interleukin-3 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007958:Leukocyte Count; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013535:Suspensions
D003115:Colony-Stimulating Factors; D004338:Drug Combinations; D006133:Growth Substances; D007074:Immunoglobulin G; D007377:Interleukin-3; D011994:Recombinant Proteins; D013535:Suspensions; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor