Targeting Th2 cytokines in fibrotic diseases

Fibrosis is characterized by the excessive accumulation of extracellular matrix components, leading to tissue scarring. Fibrosis can occur in various tissue and organ systems, and is considered a leading cause of morbidity and mortality. Because of unsatisfactory results with currently available therapies for fibrotic diseases, the development of new therapies that target fibrosis directly is warranted. This review focuses on the importance of an imbalance in T-helper type 1 (Th1)/Th2 cell responses in fibroproliferation in several major fibrotic diseases, and discusses the prospects of novel therapeutic options targeting the Th2-type inflammatory response and cytokines. With the aim of shifting the immune response toward Th1 and IFNγ responses, antagonists of IL-4, IL-5 and IL-13 have been investigated as candidate therapies for fibrogenic conditions. Several clinical trials with such cytokine antagonists are underway, but have yet to demonstrate improvements in therapeutic outcomes compared with existing therapies; however, based on the evidence available, cytokine therapies should remain the focus in fibrotic diseases, with the aim of improving the outcomes of patients.