Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications

Abstract

Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients' quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Most of the molecular targeted biological therapies developed over the last two decades were based on evidence that specific cytokines may be involved in these immune diseases. Despite pro-inflammatory cytokine pathways sharing the pathogenesis of both articular and gut diseases (i.e., tumor necrosis factor and interleukin-23), several other cytokines (i.e., interleukin-17) may be differently involved in the tissue damage process, depending on the specific disease and the organ involved in inflammation, making difficult the identification of a therapeutic plan that is efficacious for both inflammatory manifestations. In this narrative review, we comprehensively summarize the current knowledge on cytokine involvement in spondyloarthritis and inflammatory bowel diseases, underlining similarities and differences among their pathogenetic pathways; finally, we provide an overview of current and potential future treatment strategies to simultaneously target both articular and gut immune disorders.

Keywords: cytokine; gut–joint axis; inflammatory bowel diseases; psoriatic arthritis; rheumatoid arthritis; spondyloarthritis.

Figure 1

Red flags proposed for referral between gastroenterogists and rheumatologists for early diagnosis of coexisting inflammatory bowel disease (IBD) and spondyloarthritis (SpA) [6].

Figure 2

The gut–joint axis in the pathogenesis of IBD and SpA/PsA. Immunological changes in the gut–joint axis: genetic predisposition, environmental factors, and dysbiosis contribute to the loss of intestinal permeability, with consequent activation of immune cells and production of cytokines (i.e., TNF, IL-23, and IL-17), which stimulate chronic inflammation and migration of leukocytes from the gut toward the joints.