Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13

Type 2 cytokine responses are typical of immune reactions to parasitic helminth infections, allergies, and asthma, and are characterised by the production of the cytokines interleukin (IL)-4, IL-5, IL-9, and IL-13 by subsets of T helper type 2 (Th2) cells. These cytokines form a complex network of molecular and cellular interactions that mediate protective immunity to worm infection, but also induce inappropriate inflammatory responses to allergic challenge. Although considerable attention has been given to the roles played by IL-4 in Th2 responses, the identification of the related cytokine IL-13 has led to a re-evaluation of how these two molecules combine in the generation of Th2 immunity. Recent reports have highlighted that in certain challenges, IL-4 and IL-13 act in combination to ensure the rapid onset of a Th2-like response. However, these studies have also identified specific responses that are attributable to the individual cytokines. For example, IL-13 appears to play a more dominant role than IL-4 in the expulsion of certain gastrointestinal parasites. In contrast, following schistosome infection, IL-13 induces a detrimental hepatic fibrosis, while IL-4 protects against endotoxemia. These results emphasise the complexity of the cytokine network, and highlight the care that needs to be taken when designing therapeutic intervention.