Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages.

In an earlier article, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) inhibits electron transport in the respiratory chain and uncouples oxidative phosphorylation, and postulated that these effects are probably involved in its antitumor activity. We now report the effect of SYD-1 on certain macrophage functions, considering the important role of these cells in inflammatory response and also the relevant anti-inflammatory activity reported for some sydnones. Incubation of macrophages with SYD-1 (5-100 μM) for 48 h did not affect the cell viability up to a concentration of 50 μM. However, at the highest concentration (100 μM), the compound decreased macrophage viability by 20%. In assays involving 2 h and 24 h of incubation, SYD-1 (5-100 μM) did not affect the cell viability. The incubation of macrophages with the compound for 2 h promoted a dose-dependent reduction of phagocytic activity of up to ~65% (100 μM). SYD-1 (100 μM) was also able to increase the production of superoxide anion (50%). In the absence of LPS, SYD-1 decreased NO production dose-dependently by up to ~80% (100 μM). When SYD-1 and LPS were incubated concomitantly, the decrease of NO promoted by SYD was the most pronounced, reaching up to ~98% at the same concentration (50 μM). SYD-1 dose-dependently suppressed IL-6 secretion by LPS-stimulated macrophages, reaching up to ~90% of inhibition at the highest concentration (100 μM). These results indicate that SYD-1 promotes effects similar to those described for anti-inflammatory and immunosuppressive drugs, thus motivating further studies to clarify the mechanisms involved in this activity.