The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women

• Published in: Scientific reports Vol. 11; no. 1; p. 15391
• Main Authors: Vasilev, Georgi, Manolova, Irena, Ivanova, Mariana, Stanilov, Iskren, Miteva, Lyuba, Stanilova, Spaska
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/250/127; 631/250/249; 631/250/38; Autoimmune diseases; Cytokines; Enzyme-linked immunosorbent assay; Females; Helper cells; Humanities and Social Sciences; Inflammation; Interleukin 12; Interleukin 18; Interleukin 23; Interleukin 6; Lymphocytes T; multidisciplinary; Patients; Rheumatoid arthritis; Science; Science (multidisciplinary); Serum levels; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-94841-x

We aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p  = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.