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>Preclinical safety studies with recombinant human interleukin 6 (rhil‐6) in the primatecallithrix jacchus(marmoset): Comparison with studies in rats
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Preclinical safety studies with recombinant human interleukin 6 (rhil‐6) in the primatecallithrix jacchus(marmoset): Comparison with studies in rats
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机译：Preclinical safety studies with recombinant human interleukin 6 (rhil‐6) in the primatecallithrix jacchus(marmoset): Comparison with studies in rats
AbstractThe 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 μg kg−1day−1over 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 μg kg−1day−1s.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.In conclusion, despite the pleiotrophic effects of IL‐6 observedin vitro, prolonged administration of rhIL‐6 induced quite a selective stimulation of thrombopoiesis and the immune system, which were not associated with any major adverse effect in the two animal species. Since neutralizing antibodies developed against rhIL‐6 in both species within 2–4 weeks, which abolished the biological effect of IL‐6, the conductance of long‐term studies with rhIL‐6—especially on poss
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