CYTOKINE LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS: AN ASSOCIATION WITH LUNG INJURY

Abstract

The basis for the pathogenesis of rheumatoid arthritis (RA) is an imbalance in the production of proinflammatory and anti-inflammatory cytokines, which may favor the development of systemic manifestations, interstitial lung injury (ILI) in particular.Objective: to study cytokine concentrations in RA patients with and without ILI.Subjects and methods. The investigation enrolled three groups. Group 1 included 20 RA patients with ILI; Group 2 comprised 30 RA patients without ILI and Group 3 consisted of 28 healthy donors. All the RA inpatients were treated at the V.A. Nasonova Research Institute of Rheumatology. The diagnosis of RA was made on the basis of the 1987American College of Rheumatology (ACR) criteria. The serum concentrations of 27 cytokines were determined utilizing multiplex xMAP technology with a Bio-Plex200 analyzer (Bio-Rad, USA). Lung computed tomography (CT) with a GE Light Speed VCT spiral CT scanner (with a section thickness of 0.65 mm) was carried out to detect ILI.Results. As compared with the healthy donors, the RA patients with and without ILI were observed to have significantly elevated concentrations of interleukin 5 (IL-5), IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-15, eotaxin, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), macrophage inflammatory protein-1β, platelet-derived growth factor BB, RANTES, and tumor necrosis factor-α. In the RA patients with ILI, the concentrations of IL-4 and IFN-γ-inducible protein proved to be higher than in the othergroups; however, these differences reached statistical significance compared to only the healthy donors (p = 0.04 and p = 0.001, respectively). The RA patients with ILI were found to have a significant increase in IL-10 and IFN-γ levels as compared to those without ILI and the healthy donors (p = 0.008 and p = 0.0003; p = 0.0001 and p = 0.0001, respectively). Vascular endothelial growth factor concentrations were found to be lower in the RA patients with ILI than in the healthy donors (p = 0.05).Conclusion. The RA patients with ILI show a predominance of a Th2 immune response. The found activation of humoral antigen-specific immune response regulators, such as IL-4, IL-5, IL-6, IL-10, and IFN-γ, substantiates the use of anti-B-cell therapy for this type of the disease.

Keywords

• rheumatoid arthritis
• interstitial lung injury
• cytokines
• multiplex analysis