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Preclinical safety studies with recombinant human interleukin 6 (rhIL-6) in the primate Callithrix jacchus (marmoset): comparison with studies in rats.
Journal article

Preclinical safety studies with recombinant human interleukin 6 (rhIL-6) in the primate Callithrix jacchus (marmoset): comparison with studies in rats.

  • Ryffel B University of Zurich, Institute of Toxicology, Switzerland.
  • Weber M
  • 1995-01-01
Published in:
  • Journal of applied toxicology : JAT. - 1995
Acute-Phase Proteins
Animals
Basophils
Biological Availability
Blood Cell Count
Blood Platelets
Bone Marrow
Bone Marrow Cells
Callithrix
Drug Evaluation
Female
Humans
Immune System
Immunoglobulins
Injections, Subcutaneous
Interleukin-6
Kidney
Liver
Major Histocompatibility Complex
Male
Neutrophils
Rats
Rats, Wistar
Receptors, Interleukin-2
Recombinant Proteins
English The haemopoietic and immunostimulatory properties of recombinant human interleukin 6 (rhIL-6) might be used clinically in cancer patients. For the preclinical assessment of the safety of such a therapy, we chose the primate marmoset (Callithrix jacchus) and Wistar rats. Recombinant hIL-6 given to marmosets at doses of up to 1000 micrograms kg-1 day-1 over 4 and 9 weeks did not induce fever and was very well tolerated. Haematological alterations included a sustained two- to threefold increase of thrombocyte counts, peaking at 4 weeks, as well as an increase in neutrophils and basophils. The number of bone marrow megakaryocytes at 4 and 9 weeks was not increased, but the ploidy grade was augmented. An acute-phase protein response was observed within 24 h after the first IL-6 administration, which reached a maximum after 1 week. The acute-phase protein response was not accompanied by functional or morphological signs of hepatocellular damage. Increased immunoglobulin and soluble IL-2 receptor in the serum levels reflected systemic immunostimulation. Recombinant hIL-6 was also given to rats at 500 micrograms kg-1 day-1 s.c. for 4 weeks, where it induced a stimulation of thrombopoiesis associated with increased platelet counts within 1 week. Furthermore, rhIL-6-treated rats had signs of immunostimulation and increased acute-phase reactants in serum, as in marmosets. There was no evidence of renal glomerular or hepatic pathology.(ABSTRACT TRUNCATED AT 250 WORDS)
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/185516
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