Anti‐inflammatory benefits of retinoids: retinoic acid and oxidatively‐transformed β‐carotene induce neutrophil apoptosis and inhibit leukotriene B4 synthesis

Abstract

Clearance of apoptotic neutrophils following infection is critical for the resolution of inflammation. Little is known about the effects of retinoid products (vitamin A derivatives) in innate immune cells in the context of an inflammatory response.HypothesisRetinoic acid (RA) or oxidatively‐transformed β‐carotene (OxβC), a retinoid derivative, may have immuno‐modulatory benefits by promoting neutrophil apoptosis and inhibiting proinflammatory signaling.AimTo evaluate the effects of RA and OxβC in model of Mannheimia haemolytica‐induced bovine respiratory disease, a disease associated with severe inflammation.ResultsIn vitro, RA and OxβC dose‐dependently induced apoptosis, but not necrosis, in circulating bovine neutrophils, but not in epithelial cells. In M. haemolytica‐challenged calves (2×107 CFU), animals that received a 28‐day dietary OxβC treatment (10 mg/kg) had elevated apoptotic leukocytes and reduced LTB4 levels in their lower airways 3 h post‐infection versus infected‐untreated calves.ConclusionRA and OxβC promote cell‐selective apoptosis and inhibit the synthesis of proinflammatory LTB4, which in turn may confer yet unrecognized anti‐inflammatory benefits. Supported by NSERC.