Major anti-inflammatory cytokines and interleukin 6 in patients with rheumatoid arthritis: relationships and clinical significance
Authors:   Yaroslavl State Medical University, Ministry of Health of the Russian Federation, Yaroslavl, Russia, Baranov A.A. , Lapkina N. A. ,   Yaroslavl State Medical University, Ministry of Health of the Russian Federation, Yaroslavl, Russia, Shutov A. S. ,   Yaroslavl State Medical University, Ministry of Health of the Russian Federation, Yaroslavl, Russia, Levshin N. Yu. ,   Yaroslavl State Medical University, Ministry of Health of the Russian Federation, Yaroslavl, Russia, Konovalov K. M ,   Yaroslavl State Medical University, Ministry of Health of the Russian Federation, Yaroslavl, Russia, Artyukhov A. S. ,   Pirogov Russian National Research Medical University, Moscow, Russia
Published: December 2024

In the pathogenesis of rheumatoid arthritis (RA), an important role is played by dysfunction between the production of the main anti-inflammatory interleukins (IL) IL-4, IL-10 and proinflammatory (IL-6) cytokines.
Objective. Determination of IL-4, IL-6 and IL-10 concentrations in RA patients with advanced stage of the disease, assessment of the relationship between them, clinical indices of disease activity, the presence of rheumatoid factor (RF) and antibodies to cyclic citrullinated peptide (CCP).
Material and methods. The study included 154 RA patients (41 males and 113 females) of middle age (56.0 (50.0; 64.0) years), disease duration (9.4 (3.0; 13.0) years), seropositive 129 (83.8 %) for IgM RF and/or 106 (68.8 %) ACPP with moderate or high (DAS28-ESR –
5.40 (4.65; 6.00)) disease activity. The concentration of IL-4, IL-6, IL-10 in the blood serum was determined by multiplex technology.
Results. In patients with RA, the concentration of IL-4 did not differ significantly from the control, and for IL-6 and IL-10 it was significantly higher than in donors. High values of IL-6 were significantly more common (51.6 %) than IL-4 (12.33 %, p = 0.001) and IL- 10 (16.23%, p = 0.001). Reliable correlations were found between the hyperproduction of IL-4 and IL-6, IL-6 and IL-4, IL-10. For IL-4 and IL-10, such an association was not found. The concentration and frequency of increased IL-4, IL-6, IL-10 did not differ in patients positive or negative for IgM RF. The concentration of IL-4 was significantly higher in the group of patients seronegative for ACPA compared to seropositive ones, and the prevalence of high IL-4 values was also noted in this group. No such association was found for IL-6 and IL-10. The concentration of IL-6 significantly positively correlated with the indices (DAS28-ESR, CDAI, SDAI) of clinical activity of RA, and the level of IL-4 was positively associated with CDAI, SDAI, IgM RF and inversely with ACPA values. The concentration of IL-10 was associated with CDAI, SDAI, IgM RF.
Conclusion. In patients with RA in the advanced stage of the disease, the production of IL-6 predominates over the production of IL-4 and IL-10. In the presence of interrelations between these cytokines, there are certain differences in the associations with clinical indices and laboratory indicators of disease activity, IgM RF and ACPA.