Modulation of nitric oxide production in RAW 264.7 cells by transforming growth factor-beta and interleukin-10: differential effects on free and encapsulated immunomodulator

The mouse macrophage cell line RAW 264.7 can be stimulated to produce nitric oxide (NO) by muramyltripeptide cholesterol included within biodegradable poly(D,L‐lactide) nanocapsules (NC MTP‐Chol). The aim of this work was to determine whether one or both of the cytokines transforming growth factor‐beta (TGF‐β) and interleukin‐10 (IL‐10) could be responsible for feedback control seen at high concentrations. Activated RAW 264.7 cells produced TGF‐β1. When exogenous TGF‐β1 was added during stimulation, a dose‐dependent inhibition of NO production was observed when NC MTP‐Chol was used, whereas activation by the soluble muramyl dipeptide (MDP) was not affected. Furthermore, addition of a blocking antibody to TGF‐β arrested the fall in NO production seen at high concentrations of NC MTP‐Chol. Addition of IL‐10 during RAW 264.7 cell activation also reduced NO production; however, in this case, both NC MTP‐Chol and MDP were equally affected. The presence of anti‐IL‐10 antibody during activation significantly increased NO production. J. Leukoc. Biol. 62: 374–380; 1997.