Recombinant human interleukin 6 is a potent inducer of the acute phase response and elevates the blood platelets in nonhuman primates.
Human interleukin 6 (IL-6) produced by molecular cloning was administered to nonhuman primates to assess its biological activities in vivo. Rhesus monkeys were treated s.c. with recombinant human (rh) IL-6 at 3 and 30 micrograms/kg body weight/day for 11 days, followed by the administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) at 5.5 micrograms/kg/day for 5 days. Serum levels of positively regulated acute phase proteins (APP) (C-reactive protein, alpha 1-antitrypsin, haptoglobin, and ceruloplasmin) increased, whereas negatively regulated APP (prealbumin) decreased in response to rhIL-6 treatment in a dose-dependent manner. Platelet counts rose after a latent period of 4-5 days following the start of rhIL-6 treatment, resulting in a maximum twofold increase above normal levels 2-3 days after the termination of the rhIL-6 treatment. Recombinant human IL-6 treatment induced a two to threefold rise in myeloid progenitor blood cell levels. The subsequent administration of rhGM-CSF to rhIL-6-pretreated animals did not increase the progenitor cell levels in blood above those found with rhGM-CSF treatment alone, indicating that rhIL-6 compared to recombinant human interleukin 3 (rhIL-3) has a minor proliferative effect on hematopoietic precursors in vivo. In conclusion, rhIL-6 was shown to be a potent stimulator of APP and was able to increase the number of platelets in circulation in nonhuman primates.
Mayer
P
P
Sandoz Forschungsinstitut, Vienna, Austria.
Geissler
K
K
Valent
P
P
Ceska
M
M
Bettelheim
P
P
Liehl
E
E
D000210:Acute-Phase Reaction / Q000097:blood*; D000818:Animals; D000906:Antibodies / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006242:Haptoglobins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology*; D007958:Leukocyte Count; D008253:Macaca mulatta; D008297:Male; D010976:Platelet Count; D011228:Prealbumin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000906:Antibodies; D006242:Haptoglobins; D007074:Immunoglobulin G; D015850:Interleukin-6; D011228:Prealbumin; D011994:Recombinant Proteins; D000515:alpha 1-Antitrypsin; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D002570:Ceruloplasmin