Retinoid derivatives offer anti‐inflammatory benefits by promoting neutrophil apoptosis and inhibiting proinflammatory mediator production in a model of bovine respiratory disease

Abstract

Clearance of apoptotic neutrophils (PMN) following infection is critical for the resolution of inflammation. Despite demonstrating immunomodulatory properties, the effects of retinoids in PMN in the context of an inflammatory response remain unknown.Objectiveto evaluate the immunomodulatory properties of two retinoids, oxidatively‐transformed carotene‐β (OxC‐β) and retinoic acid (RA) in a model of Mannheimia haemolytica‐induced bovine respiratory disease, which is characterized by severe inflammation.Resultsin vitro, RA and OxC‐β induced caspase‐and time‐dependent apoptosis, but not necrosis, in bovine PMN, but not epithelial cells or fibroblasts. Neither RA nor OxC‐β affected PMN function. In M. haemolytica‐infected calves (2×107 CFU), animals that received a 28‐day dietary OxC‐β treatment (10 mg/kg) had elevated apoptotic leukocytes and reduced LTB4 levels in their lower airways 3h post‐infection vs infected‐untreated calves.ConclusionRA and OxC‐β promote cell‐specific apoptosis and inhibit the production of pro‐inflammatory LTB4, both mechanisms that promote the resolution of inflammation, thereby suggesting an anti‐inflammatory role for retinoid derivatives. Supported by NSERC and AIHS.