Tumor necrosis factor and Interleukin-17 inflammatory pathway components (TNF/IL-17 axis)

The TNF and IL-17 inflammatory pathway components constitute a synergistic signaling network that plays a central role in the pathogenesis of chronic autoimmune and inflammatory diseases [3, 6]. Tumor Necrosis Factor (TNF) and Interleukin-17 (IL-17, specifically IL-17A and IL-17F) are pro-inflammatory cytokines that cooperatively amplify the immune response by inducing the production of secondary mediators, such as IL-6, IL-8, and matrix metalloproteinases, in various cell types including keratinocytes and synoviocytes [3, 7, 10]. This synergy is a key driver of tissue destruction and persistent inflammation in conditions such as psoriasis, psoriatic arthritis, and rheumatoid arthritis [1, 4, 9]. While monotherapies targeting either TNF or IL-17 are highly effective, some patients remain refractory, leading to the development of dual-targeting agents like bispecific antibodies that neutralize both pathways [5, 8, 13]. However, therapeutic inhibition of these components carries risks, most notably an increased susceptibility to serious infections and specific challenges such as fungal candidiasis associated with IL-17 blockade [8, 11].

Other names

TNF and IL-17 pathwayTNF/IL-17 synergistic axisIL-17/TNF-alpha signaling pathwayTumor necrosis factor and Interleukin-17 axis

Neutralization of TNF-alpha and IL-17 (A and/or F) cytokines or blockade of their respective receptors to inhibit synergistic pro-inflammatory signaling and downstream gene expression [1, 5, 10].