MCP‐1 −/− Mice Show Blunted Inflammatory Cytokine Response and Improved Recovery Following Exercise‐Induced Muscle Damage

Abstract

The body's inflammatory response to eccentric‐biased exercise in both brain and muscle contributes to impaired performance recovery. Monocyte chemoattractant protein (MCP‐1) is essential in the release of inflammatory mediators, but its role in exercise‐induced muscle damage has not yet been determined. The purpose of this study was to determine the role of MCP‐1 on brain and muscle inflammation following a novel bout of downhill running. C57BL/6 (n=24) and MCP‐1−/− mice (n=24), 8 weeks of age were randomly assigned to one of six groups: downhill runner wild type (DH‐WT), uphill runner wild type (UH‐WT), sedentary wild type (WT), downhill runner MCP‐1−/− (DH‐MCP‐1−/−), uphill runner MCP‐1−/− (UH‐MCP‐1−/−), and sedentary MCP‐1−/− (MCP‐1−/−). The mice were run on a treadmill at −/+14% grade and 22m/min, for 150 min. Mice were sacrificed at 24h post downhill run, and the brain and gastrocnemius muscle (G) were dissected and analyzed for IL‐1β, IL‐6, TNF‐α and F4/80 mRNA using RT‐PCR. Gene expression of IL‐1β, IL‐6 and TNF‐α was increased in the cerebellum, cortex and G in DH‐WT relative to WT (p<0.05), whereas DH‐MCP‐1−/− was not different from WT. A similar effect was observed for F4/80 but this reached statistical significance in G only (p<0.05). No differences were found in any other groups. These data support a necessary role for MCP‐1 following exercise‐induced muscle damage.Supported by a grant from NASA and ACSM.