Abstract
Purpose Rheumatoid arthritis (RA) is an often debilitating autoinflammatory disease. Patients with rheumatoid arthritis are often troubled by co-occurring depression or other psychological manifestations. RA patients have a variety of treatment options available, including biologicals that inhibit cytokines or immune cells. If these cytokines influence the psychological symptoms, then the use of cytokine inhibitors should modulate these symptoms. Methods A cohort of 209 individuals was recruited. This group included 82 RA patients, 22 healthy subjects, 32 depressed control subjects, and 73 subjects with systemic lupus erythematosus. Of the RA patients, 51% were on a biological therapeutic. ELISA was used to measure cytokine levels. A variety of psychological assessments were used to evaluate depression, anxiety, sleep, fatigue, and relationship status. Clinical values were obtained from medical records. Results IL-10 concentration was associated with depressive symptoms in the RA patients, healthy controls, and the lupus patients. In the patients with primary depression, depressive symptoms were associated with IL-6 and TNF-alpha. In RA patients, Tocilizumab use was associated with decreased depressive symptoms. 14 RA patients who were not using biologicals began using them by a one-month follow-up. In these patients, there was no significant change to any value except for fatigue. Conclusions A variety of both biological and social factors influences depressive symptoms in RA. IL-10 and IL-6 are likely to be involved, since IL-10 concentration was associated with depression and Tocilizumab decreased depressive symptoms in the RA patients. The roles of these cytokines are different in RA and lupus, as high IL-10 in RA is associated with increased depressive symptoms, but high IL-10 in the lupus patients is associated with decreased depression. IL-6 was also associated with depressive symptoms in the patients with primary depression. These results strongly indicate that disease activity, including cytokine levels, has a strong impact on depressive symptoms.
Highlights
Rheumatoid arthritis (RA) is a destructive autoinflammatory arthritis characterized by the overproduction of certain proinflammatory cytokines
The roles of these cytokines are different in RA and lupus, as high IL-10 in RA is associated with increased depressive symptoms, but high IL-10 in the lupus patients is associated with decreased depression
In order to investigate the role of cytokines in depression associated with rheumatoid arthritis, we studied the relationship between depression, clinical markers, and serum cytokine levels in rheumatoid arthritis patients, patients being treated for primary depression, healthy controls, and lupus patients
Summary
Rheumatoid arthritis (RA) is a destructive autoinflammatory arthritis characterized by the overproduction of certain proinflammatory cytokines. Treatment with monoclonal antibodies or antibody derivatives (biologicals) that block specific cytokines has been very successful. Many of these biologicals prevent bone destruction and have a substantial impact on Journal of Immunology Research disease activity [1]. Patients with rheumatoid arthritis have a higher prevalence of depression and anxiety than the general population [2] Part of this increased prevalence may be due to the toll that chronic, painful disease takes on the quality of life. Another aspect may be the heightened levels of inflammatory cytokines found in rheumatoid arthritis. Depression may influence cytokine activity, as patients with more depressive symptoms are less responsive to biological antirheumatic therapies [10]
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