Antigenic stimulation is more efficient than LPS in inducing nitric oxide production by human mononuclear cells on the in vitro granuloma reaction inschistosomiasis

Nitric oxide (NO) is an extremely important and versatile messenger in biol ogical systems, It has been identified as a cytotoxic factor in the immune system, presenting anti- or pro-inflammatory properties under different cir cumstances. In murine monocytes and macrophages, stimuli by cytokines or li popolysaccharide (LPS) are necessary for inducing the immunologic isoform o f the enzyme responsible for the high-output production of NO, nitric oxide synthase (iNOS), With respect to human cells, however, LPS seems not to st imulate NO production in the same way. Addressing this issue, we demonstrat e here that peripheral blood mononuclear cells (PBMC) obtained from schisto somiasis-infected patients and cultivated with parasite antigens in the in vitro granuloma (IVG) reaction produced more nitrite in the absence of LPS. Thus, LPS-induced nitrite levels are easily detectable, although lower tha n those detected only with antigenic stimulation. Concomitant addition of L PS and L-N-arginine methyl eater (L-NAME) restored the ability to produce d etectable levels of nitrite, which had been lost with L-NAME treatment. In addition, LPS caused a mild decrease of the IVG reaction and its associatio n with L-NAME was responsible for reversal of the L-NAME-exacerbating effec t on the IVG reaction. These results show that LPS alone is not as good an NO inducer in human cells as it is in rodent cells or cell Lines. Moreover, they provide evidence for interactions between LPS and NO inhibitors that require further investigation.