N-[3-(Aminomethyl)benzyl]acetamidine (1400 W) as a Potential Immunomodulatory Agent

Abstract

This study was designed to investigate the relationship between NO, IL-12, and TNF-αproduction by J774A.1 macrophages activated with LPS and IFN-γin the presence of N-[3-(aminomethyl)benzyl]acetamidine (1400 W). 1400 W is a novel, highly selective inhibitor of inducible nitric oxide synthase (iNOS). We compared the obtained data with the effect of NG-monomethyl-L-arginine (L-NMMA) (a nonselective NOS inhibitor) and L-NG-(1-iminoethyl)lysine (L-NIL) (a relatively selective inhibitor of iNOS activity) on cells in this model. To investigate the involvement of an exogenous NO on IL-12 and TNF-αproduction we used NO donor—S-nitrosocaptopril (S-NO-Cap). The most potent inhibitor of NO generation was 1400 W. This compound also markedly increased IL-12 p40 secretion and decreased TNF-αrelease. L-NIL suppressed both NO and TNF-αproduction, but it did not change IL-12 p40 synthesis. The effect of L-NMMA on NO generation was weaker than other inhibitors. Moreover, it decreased TNF-αsecretion slightly but not significantly. IL-12 p40 production by stimulated cells was inhibited by S-NO-Cap in a dose dependent manner, but no effect on TNF-αrelease was observed. The potency and selectivity of 1400 W as an inhibitor of iNOS and cytokine release modifier are encouraging for therapeutic use.