The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women.
Georgi Hristov VasilevIrena M ManolovaMariana G IvanovaIskren StanilovLyuba Dineva MitevaSpaska A StanilovaPublished in: Scientific reports (2021)
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.
Keyphrases
- rheumatoid arthritis
- disease activity
- end stage renal disease
- early stage
- chronic kidney disease
- systemic lupus erythematosus
- ejection fraction
- newly diagnosed
- prognostic factors
- stem cells
- type diabetes
- peritoneal dialysis
- machine learning
- rheumatoid arthritis patients
- polycystic ovary syndrome
- patient reported outcomes
- pregnant women
- adipose tissue
- cancer therapy
- patient reported
- breast cancer risk
- single cell
- neoadjuvant chemotherapy
- high throughput