Severe acidosis affects the anti-inflammatory properties of N-acetylcysteine on lipopolysaccharide-activated macrophages

Critical illness is exemplified by a state of profound disruption in physiological homeostatic mechanisms. Tissue acidosis is an hallmark of inflammation/ischemia and tumor processes and although it remains uncertain whether there is a true cause-effect relation between acidosis and adverse clinical outcomes it remains a powerful marker of poor prognosis in critically ill patients. Patients with severe sepsis and septic shock exhibit a complex metabolic pattern of acidosis at intensive care unit admission, caused predominantly by hyperchloremic acidosis, which was more pronounced in non survivors. Abnormalities in systemic acid-base balance may also induce significant alterations in the immune response. In this study we evaluated the effect of N-acetylcysteine (NAC), an important cellular antioxidant, during severe hyperchloremic acidosis, in vitro, in Lipopolysaccharide from E.coli (LPS)-treated J774A.1 murine/macrophage cell line. Our results show that NAC, in hyperchloremic acidosis conditions, reduces nitric oxide (NO) and reactive oxygen species (ROS) release and iNOS expression. Furthermore these effects are associated to alterations in J774A.1 macrophage cell cycle distribution but not to impairments of cell viability and apoptosis induction. Our data report a reduced inflammatory response exerted by NAC in condition of hyperchloremic acidosis indicating that the use of NAC during inflammation further impairs immune response associated to acidosis associated disease, as septic shock.