Dataset Information

Going Further: Comprehensive Disease Control of Rheumatoid Arthritis, Targeting Cytokines and Chemokines.

ABSTRACT:

Objectives

Mechanism of action of biological and synthetic disease-modifying antirheumatic drugs (DMARDs) includes the inhibition of specific proinflammatory cytokines. This study aimed to elucidate the cytokines and chemokines inhibited by different treatments (conventional synthetic DMARD [csDMARD], biological and targeted synthetic DMARD) in rheumatoid arthritis (RA).

Methods

Fifty-nine RA patients with low disease activity or remission included in a cross-sectional study were classified by treatment in groups: abatacept, certolizumab, rituximab (RTX), tocilizumab, tofacitinib (TOF), baricitinib (BAR), and csDMARD. Cytokine and chemokine serum levels were measured by LEGENDplex Human Inflammation panel. Quantitative variables were compared using Student t or Mann-Whitney U test as appropriate, whereas qualitative variables were compared using χ2 or Fisher exact test. p < 0.05 was considered significant.

Results

Certolizumab, RTX, tocilizumab, and TOF showed that most cytokine pathways inhibited: tumor necrosis factor α, interferon γ, interleukin 1β (IL-1β), IL-12, IL-18, and IL-23; in addition, csDMARDs showed a similar inhibition patron except for IL-23. Serum level of tumor necrosis factor α pathway was one of the most inhibited being undetectable in RTX, TOF, and BAR groups. Interleukin 6 was shown to be inhibited by abatacept, RTX, and TOF; however, higher levels were observed in 3 patients treated with tocilizumab. Abatacept, certolizumab, RTX, and TOF downregulated IL-10 in this group of patients but remained detectable in almost half of the subjects, with the highest levels in the BAR group. The active pathways that remained the most were CC chemokine ligand 2, IL-8, IL-17, and IL-33.

Conclusions

Understanding the cytokine chemokine pathways inhibition could help rheumatologists to prescribe a tailored therapy using the arsenal of DMARDs for individualized RA treatment in an evidence-based decision manner.

SUBMITTER: Chavarria-Avila E

PROVIDER: S-EPMC8612915 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeRheumatoid 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.MethodsA 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.ResultsIL-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.ConclusionsA 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.