Do cytokines affect development of fatigue in rheumatoid arthritis patients?

Chronic illnesses are associated with an increased risk of fatigue. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with accumulation of inflammatory mediators in the joint space. Fatigue is a common co morbidity disorder with RA, which leads to worsened health outcomes, and is hypothesized to be strongly associated with systemic inflammation, particularly with dysregulation of the cytokine network. This study aimed to determine the development of fatigue depending on different proinflammatory cytokines. Overall 30 RA patients were included in the study: 23 females (76.7%) and 7 male (23.3%) with the average age 59.5±11.2 (ranging from 39 to 79). To achieve the goal, patients were interviewed using adapted semi-structured interview questions created by Minnock et.al. (2016) and cytokine panel (TNF-α, INF-g, IL-2, IL-6, IL-17A, IL-21, IL-23) was created to determine the differences in their levels using the Luminex200 system. Based on the results of the survey, RA patients were divided into two groups - with and without fatigue. In both the fatigue and non-fatigue RA patient groups, a positive association was found between IL-17 and INF-g, IL-17 and IL-2, and also between INF-g and IL-2, IL-21 and IL-23 levels (in all cases r> 0.7, R2> 0.5). In the fatigue group of RA patients, INF-g was positively correlated with IL-21, IL-23 and TNF-α levels, as well as IL-23 with IL-2 and IL-2 with TNF-α. In turn, both positive (with IL-2) and negative (with TNF-α) association was detected in IL-21 (R2> 0.5 for all pairs). In the group of RA non-fatigue patients, a positive association was found only between IL-17 and IL-21, IL-17 and IL-6, as well as between INF-g and IL-6 levels (R2> 0.5). The presented data suggest that only IL-6 doesn’t significantly affect the development of fatigue in RA patients.