IL-17 axis bridges psoriasis and metabolic syndrome, driving systemic inflammation and cardiometabolic dysfunction

Psoriasis is a chronic inflammatory skin disease increasingly recognized for its strong association with a cluster of cardiometabolic comorbidities, including obesity, type 2 diabetes, and cardiovascular disease. Current treatments often focus on cutaneous symptoms, but fail to adequately address the systemic inflammatory burden. The interleukin-17 (IL-17) signaling axis has emerged as a central player, not only driving skin inflammation but also contributing to the systemic metabolic dysfunction observed in these patients, highlighting a critical gap in holistic therapeutic approaches.

This review systematically examined the complex immunometabolic interactions mediated by the IL-17 axis. The authors investigated how IL-17, in synergy with other key cytokines such as TNF-α, IL-6, IL-1β, IL-23, and various adipokines, contributes to the development of endothelial dysfunction, insulin resistance, and adipose-tissue inflammation. The review synthesized existing literature to elucidate the molecular pathways linking cutaneous inflammation to systemic metabolic derangements in psoriasis patients.

Beyond its well-established role in psoriasis pathogenesis, the IL-17 pathway is deeply implicated in the 'psoriatic march,' a process linking chronic skin inflammation to accelerated atherosclerosis. The review highlights that the advent of IL-17 inhibitors has revolutionized the management of moderate-to-severe psoriasis, achieving unprecedented skin clearance, often reaching PASI 90/100 scores. Emerging evidence suggests that these agents may also exert potential beneficial effects on selected inflammatory and cardiometabolic markers. However, their direct impact on overall metabolic parameters, such as HbA1c or lipid profiles, remains an active area of investigation. This dual role underscores the IL-17 axis as a critical target for addressing both skin and systemic manifestations.

The IL-17 pathway is a key driver of both cutaneous inflammation and systemic metabolic dysfunction, linking psoriasis to comorbidities like obesity and type 2 diabetes.