Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics

Abstract

The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-γ, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-α in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA.

Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption

“…It is overexpressed in many tumors and cancer cell lines, and promotes tumor growth, angiogenesis, and metastasis in a variety of human cancers [161]. It is also elevated in the serum and synovial fluid of RA patients [162]. Production of IL-8 by breast cancer cells increases osteoclast formation and may contribute to bone metastasis [163].…”

Mangosteen ethanol extract alleviated the severity of collagen-induced arthritis in rats and produced synergistic effects with methotrexate

“…However, several clinical studies showed no significant differences concerning therapeutic efficacies between the two types of medications in treating RA patients (Osiri et al. 2016 ). cDMARDs are inexpensive and efficacious, and therefore are commonly used as the first-line drugs in clinical practice until now.…”

Role of Secreted Frizzled-Related Protein 1 and Tumor Necrosis Factor-α (TNF-α) in Bone Loss of Patients with Rheumatoid Arthritis

“…In this study, other subjects also used a combination of DMARD therapy. The study of Osiri et al [24], which also used a combination of 2 DMARD and 3 DMARD, showed low TNF-α level, 1.22 pg/mL and 1.44 pg/dL, respectively.…”