Genes such as Ym1 and Arginase, which are known to be regulated by IL-4 in murine macrophages (2, 3), were not detected in our study. We speculated that these differences may reflect the fact that IL-4 and IL-13 are highly similar yet different molecules (4, 5).

In their letter, Raes and colleagues comment on additional factors that may explain differences in the IL-4 and IL-13 gene profiles, including differences related to the type of cells investigated (eg, blood monocytes vs differentiated macrophages) or related to the species investigated (ie, human vs mouse). We completely agree with Raes and colleagues, and we also believe that multiple factors may be responsible for the discrepancies reported (1) and different explanations might be found for any single gene investigated. In relation to the differential induction of Arginase in our experimental conditions and those reported by others (2, 3), it is likely that the explanation is in the interspecies differences between human cells and mouse macrophages. In fact, in a gene profile of human monocytes, monocyte-derived dendritic cells and monocyte-derived macrophages polarized to the M1 phenotype (LPS or immunocomplexes) or the M2 phenotype (IL-4 or IL-13)(6), we also have not found an up-regulation of Arginase (our unpublished observations). An integrated analysis of the transcriptomes in different experimental conditions will provide further evidence on the level of regulation of monocyte and macrophage-regulated genes. Therefore, we certainly agree with the note of caution that Raes and colleagues have pointed out.