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.
Yao et al. now suggest that the regulation of another cytokine—IL-10—may explain these perplexing observations. They show that dendritic cells (DCs) stimulated in the presence of IL-4 made less IL-10 than those stimulated without IL-4. As a result, the IL-4–treated DCs produced more of the Th1-polarizing cytokine IL-12—known to be inhibited by IL-10—and polarized naive T cells toward a Th1 phenotype more effectively. IL-10 was critical for the increased Th1 response, as IL-4 did not increase IL-12 production or T cell polarization by IL-10–deficient DCs.
IL-4 had the opposite effect on B cells, provoking increased IL-10 production. The authors suggest that the differential effect of IL-4 at different times during infection may reflect a switch from DCs to B cells as the predominant cell type that is presenting antigen.