IL-6 Differs from TNF-α: Unpredicted Clinical Effects Caused by IL-6 Blockade in Psoriasis

IL-6 is a pleiotropic proinflammatory cytokine that is elevated in serum and skin lesions of patients with psoriasis. Anti-IL-6 therapies, however, which are effective for rheumatoid arthritis, are either ineffective for psoriasis or can induce new-onset psoriasis-like disease. Fritz et al. provide a potential explanation for these clinical observations by examining IL-17C-driven psoriasis-like disease in mice with an IL-6-deficient genetic background. These mice displayed slower onset skin disease initially, but then worsened over time, suggesting that a lack of IL-6 led to compensatory proinflammatory effects by other cytokines, which eventually worsened the psoriatic inflammation.