DYNAMICS OF CYTOKINE PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS AS INFLUENCED BY INFLIXIMAB (REMIKEID) ADMINISTRATION

• Published in: Medit͡s︡inskai͡a︡ immunologii͡a Vol. 10; no. 2-3; pp. 251 - 260
• Main Authors: Zhugrova, E. S., Mazurov, V. I., Lila, A. M., Syssoev, K. A., Lapin, S. V., Totolian, Areg A.
• Format: Journal Article
• Language: English; Russian
• Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 16.07.2014
• Subjects: cytokines; das28; haq functional index; infliximab; methotrexate; rheumatoid arthritis; tnfα
• ISSN: 1563-0625; 2313-741X
• DOI: 10.15789/1563-0625-2008-2-3-251-260

Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease with predominantly destructive lesions of peripheral joints, with prevalence of 0.6 to 1.6% in general population. An important pathogenetic role in this disease is now attributed to imbalance between pro- and antiinflammatory cytokines. Clinical introduction of biological preparations, such as Infliximab (monoclonal antibodies to TNFα) within last years have changed therapeutic approach to treatment of rheumatic diseases. The aim of our research was to evaluate dynamics of pro- and antiinflammatory cytokine profile in the patients with rheumatoid arthritis (RА) during combined therapy with Infliximab and Methotrexate (MT). The study included 30 patients (27 females, 3 males, mean age of 52.5±2.0 years) who received combined therapy with МТ and Infliximab (Inx). Inx was initially injected at a single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and then repeated every 8 weeks. Regular examination of the patients included clinical and laboratory studies (ESR, levels of IL-6, IL-8, TNFα, IL-4, IL-10, GSM-CSF, IFNγ). Levels of antibodies against Infliximab in the groups of RА patients were determined before treatment and 22 weeks later. Efficiency of the therapy was estimated according to DAS28 3V Index and to HAQ Questionnaire.Upon decreased activity of disease, as assessed by DAS28, and improvement of HAQ parameters, a marked decrease in proinflammatory cytokine levels (IL-6, IL-8, TNFα) was detected, that confirming a pathogenetic significance of cytokine in RА patients. In patients with marked clinical effect (group I), an initially normal contents of TNFα was found in blood serum, and this group showed better response to Infliximab therapy, than groups II and III (resp., moderate and absent response) with initially high contents of TNFα and other cytokines, that was proven by correlations with ACR criteria and HAQ functional index. These events were accompanied by more significant improvement of RА course and increased functional abilities of joints. In patients from group III (absence of clinical effects), the level of antibodies to Infliximab before therapy was high, and it was increased by 22 week of treatment. It was shown that, in cases of initially high levels of endogenous anti-TNFα antibodies, clinical response to Infliximab therapy is likely to be reduced. Thus, it is possible to suggest that determination of initial TNFα and IL-10 levels, as well as starting levels of antibodies to Infliximab, and their changes in the course of therapy can be used as immunological parameters, thus allowing to predict the responses to Infliximab therapy. (Med. Immunol., 2008, vol. 10, N 2-3, pp 251-260).