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Pathology induced by interleukin-6

B Ryffel1, M J Mihatsch, G Woerly

  • 1Institut für Toxikologie, Eidgenössischen Technischen Hochschule Universität Zürich, Switzerland.

International Review of Experimental Pathology
|January 1, 1993
PubMed
Summary
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High-dose recombinant human interleukin-6 (rhIL-6) stimulated immune and blood cell production in mice, rats, and primates. Despite an acute-phase response, no significant organ damage was observed, though antibodies formed.

Area of Science:

  • Immunology
  • Hematology
  • Pharmacology

Background:

  • Interleukin-6 (IL-6) is a key cytokine involved in immune responses, blood formation (hemopoiesis), and host defense.
  • Understanding the effects of therapeutic IL-6 administration is crucial for its clinical application.

Purpose of the Study:

  • To evaluate the biological effects and safety profile of high-dose recombinant human interleukin-6 (rhIL-6) in animal models.
  • To assess the immunostimulatory, hemopoietic, and potential toxicological impacts of rhIL-6.

Main Methods:

  • Administration of high-dose rhIL-6 to mice, rats, and nonhuman primates.
  • Monitoring of immune response, hemopoiesis (particularly megakaryocytes), and acute-phase reactions.
  • Histopathological examination of major organs, including the liver, and assessment for glomerular pathology.

Related Experiment Videos

  • Detection of neutralizing antibodies against rhIL-6.

    • Main Results:

    • rhIL-6 demonstrated immunostimulatory and hemopoietic effects across all species, notably enhancing megakaryocyte production.
    • Nonhuman primates exhibited the most pronounced acute-phase response without significant liver histopathology.
    • No evidence of glomerular pathology was detected in any of the tested species.
    • Neutralizing antibodies to rhIL-6 were generated in all species within 10 days of administration.

    Conclusions:

    • High-dose rhIL-6 exhibits potent immunostimulatory and hemopoietic effects with a generally favorable safety profile in preclinical models.
    • The cytokine induces an acute-phase response, particularly in primates, but without significant organ toxicity.
    • The development of neutralizing antibodies suggests potential limitations for long-term or repeated rhIL-6 therapy.