[Role of interleukin-4 in the regulation of nitric oxide production by normal human monocytes].

: Resting normal human monocytes were found to produce small amounts of cGMP in response to IL-4. This production was inhibited in the presence of LNMMA suggesting an association with activation of the NO synthase (NOS) pathway. In addition, this cGMP generation was abrogated in the presence of either a Ca2+ chelator, EGTA, or a calcium/calmodulin inhibitor, W7, suggesting that IL-4 stimulates the constitutive NOS (cNOS). An enhanced response was observed when monocytes were preincubated with IFN-gamma and whether the cGMP accumulation was still abrogated in the presence of LNMMA it was not affected by either EGTA or W7 suggesting, in that case, the activation of an inducible NOS (iNOS). Taken together these data suggest that IL-4 could stimulate a cNOS in resting and an iNOS in the IFN-gamma-treated human monocytes, indicating that the generation of NO is highly dependent on the maturation state of these cells.