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Abstract <p>Elevated systemic production of interleukin-6 (IL-6) is associated with a broad spectrum of autoimmune and inflammatory diseases. Monoclonal antibody therapies targeting IL-6 or its receptor are widely used to neutralize the accompanying adverse effects. This study addresses the challenge of independently quantifying free and olokizumab (OKZ)-bound IL-6 in biological samples using a preclinical mouse model with regulated overexpression of human IL-6. We developed an enzyme-linked immunosorbent assay (ELISA), in which biotin-labeled OKZ served as a detecting agent, enabling <i>in&#xa0;vivo</i> tracking of dynamics of IL-6/OKZ immune complexes. OKZ effectively reduced free IL-6 levels in mice with cytokine overexpression for at least 7 days, while persisting in circulation as IL-6/OKZ complexes. Additionally, we assessed the kinetics of neutralizing anti-OKZ antibody formation in this preclinical model. The methods developed can be applied for clinical monitoring during anti-cytokine therapy and in preclinical studies using mouse models to evaluate the efficacy of such therapy in controlling IL-6-dependent inflammation in experimentally induced diseases.</p>

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Detection of Free and Olokizumab-Bound Interleukin-6 during Anticytokine Therapy

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Aleksandra V. Pavlova,
  • Anna M. Litvinova,
  • Ekaterina O. Gubernatorova,
  • Anastasia S. Yakovleva,
  • Sergei A. Nedospasov,
  • Marina S. Drutskaya,
  • Irina V. Astrakhantseva

摘要

Abstract

Elevated systemic production of interleukin-6 (IL-6) is associated with a broad spectrum of autoimmune and inflammatory diseases. Monoclonal antibody therapies targeting IL-6 or its receptor are widely used to neutralize the accompanying adverse effects. This study addresses the challenge of independently quantifying free and olokizumab (OKZ)-bound IL-6 in biological samples using a preclinical mouse model with regulated overexpression of human IL-6. We developed an enzyme-linked immunosorbent assay (ELISA), in which biotin-labeled OKZ served as a detecting agent, enabling in vivo tracking of dynamics of IL-6/OKZ immune complexes. OKZ effectively reduced free IL-6 levels in mice with cytokine overexpression for at least 7 days, while persisting in circulation as IL-6/OKZ complexes. Additionally, we assessed the kinetics of neutralizing anti-OKZ antibody formation in this preclinical model. The methods developed can be applied for clinical monitoring during anti-cytokine therapy and in preclinical studies using mouse models to evaluate the efficacy of such therapy in controlling IL-6-dependent inflammation in experimentally induced diseases.