Classical proinflammatory cytokines in patients with rheumatoid arthritis: immunologic and clinical relationships

Relevance. Activation of innate and acquired immunity, accompanied by increased production of classical (interleukin (IL) IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ)) proinflammatory cytokines in synovial fluid and blood serum, plays an important role in the pathogenesis of rheumatoid arthritis (RA).

Objective. To determine the concentration of IL-1β, IL-6, TNF-α and INF-γ in RA patients in the advanced stage of the disease, to evaluate the relationship between them, clinical indices of disease activity, the presence of rheumatoid factor (RF), and antibodies to cyclic citrullinated peptide (ACCP).

Material and methods. We examined 154 patients with RA (41 men and 113) who were middle-aged (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 %) ACCP with moderate to high (DAS28-ESR — 5.40 (4.65; 6.00)) disease activity. The concentration of IL-1β, IL-6, TNF-α and INF-γ in serum determined by multiplex technology.

Results. The concentration of IL-1β was not significantly different between patients with RA and controls. The values of IL-6 and INF-γ were significantly higher, and TNF-α — significantly lower than in donors. IL-6 hyperproduction was detected most frequently (51.6 %), whereas elevated levels of INF-γ (38.96 %), IL-1β (26.62 %) and TNF-α (23.38 %) were less common. Significant positive correlations were observed between the concentrations of all cytokines and their high levels. The strongest correlations were characteristic for IL-1β, TNF-α and INF-γ. No statistically significant differences in cytokine levels were observed between patients with RA who were positive or negative for IgM-RF and ACCP. The concentration of IL-6 alone significantly positively correlated with the values of the indices (DAS28-ESR, CDAI, SDAI) of RA clinical activity (p<0.05).

Conclusions. There are differences in the levels and frequencies of proinflammatory cytokines among patients with advanced-stage RA. In the presence of a close relationship between them, there are certain differences in their associations with clinical and laboratory indicators of disease activity.

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