A study on page 1899 may explain the seemingly fickle ways of the cytokine interleukin (IL)-4. Yao and colleagues show how this quintessential T helper (Th) 2 cytokine can sometimes promote the opposite Th1 response.

The prototypic Th2 cytokine IL-4 inhibits IL-10 production by DCs, thereby increasing the production of the Th1-promoting cytokine IL-12.

IL-4 is known as the key cytokine for polarizing naive T cells toward a Th2 phenotype, which is important for antibody production and protection against parasitic infections. Under some conditions, however, IL-4 has been shown to instead induce a Th1 response. Indeed, a recent study showed that mice treated with IL-4 during initial infection with Leishmania major had increased Th1 responses and were protected. If given later, IL-4 increased Th2 responses and exacerbated disease.

Yao et al. now suggest that the regulation of another cytokine—IL-10—may explain these perplexing observations. They show...

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