Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells

Endosulfan is an organochlorine insecticide comprised of two isomers: endosulfan-α and endosulfan-β. Endosulfan exposure has been shown to elevate some inflammatory factors, such as nitric oxide (NO) and tumor necrosis factor (TNF), in animals or cultures of animal cells. Because the two endosulfan isomers can vary in their biological activities, the goal of this study was to determine if individual endosulfan isomers differentially impact production of NO or TNF by the mouse macrophage cell RAW 264.7 at non-cytotoxic levels. We found elevated TNF with exposure to endosulfan-α (not endosulfan-β), but only at concentrations that were cytotoxic (≥100 μM), whereas neither endosulfan isomer altered baseline levels of NO at any concentration up to 300 μM. In interferon (IFN)-γ-activated cultures, NO levels were significantly suppressed by either endosulfan isomer at 10 μM (the lowest concentration examined), whereas only endosulfan-β significantly lowered TNF levels at non-cytotoxic concentrations. In lipopolysaccharide (LPS)-activated cultures, both endosulfan isomers significantly reduced NO, but not TNF, at non-cytotoxic concentrations. These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation.