RETRACTED: Anti-Inflammatory Effects of Chronic Aspirin on Brain Arachidonic Acid Metabolites (Retracted article. See vol. 40, pg. 1094, 2015)

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TXB2) to lipoxin A(4) (LXA(4)) and 15-epi-LXA(4). However, it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE(2), TXB2 and leukotriene B-4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE(2), but increased LTB4, LXA(4) and 15-epi-LXA(4) concentrations. Both doses attenuated the LPS effects on PGE(2), and TXB2. The increments in LXA(4) and 15-epi-LXA(4) caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA(4) and 15-epi-LXA(4) and reduce pro-inflammatory PGE(2) and TXB2 suggests considering aspirin further for treating clinical neuroinflammation.