Role of brain macrophages on IL-1 beta and fatigue following eccentric exercise-induced muscle damage

Fatigue associated with recovery from muscle damage has recently been linked to increases in brain and muscle proinflammatory cytokines. However, little is known regarding the origin of these cytokines. Since macrophage-like cells in the brain are a primary source of cytokines, we used a brain specific macrophage depletion technique involving liposome encapsulated clodronate (CLD) to examine the role of macrophages on brain IL-1 beta and fatigue following eccentric exercise-induced muscle damage. Mice were assigned to six groups: Downhill saline (DWNSAL), downhill clodronate (DWNCLD), uphill saline (UPSAL), uphill clodronate (UPCLD), non-running saline (CONSAL) or non-running clodronate (CONCLD). Mice were given intracerebroventricular (ICV) (10 mu L) injections of clodronate-filled liposomes (CLD) to deplete macrophages, or saline-filled liposomes (SAL) and run on a treadmill at 22 m/min and -14% (DWN) or 14% (UP) grade for 150 min. A subset of uphill and downhill running mice (n = 40) was then run to fatigue on a treadmill at 36 m/min, 8% grade at 24 h after the uphill and downhill runs. A second subset of uphill, downhill, and control mice (n = 30) was sacrificed 24 h after the run for analysis of brain IL-1 beta concentration. Histological examination confirmed previous reports that CLD administration reduced perivascular and meningeal macrophage subsets in the brain. CLD reduced IL-1 beta concentration in the cortex of DWN mice (P < 0.05), which was associated with enhanced treadmill performance 24 h after both uphill and downhill runs (P < 0.05) although the magnitude was greater following the downhill run. These results suggest that brain macrophages can contribute to the increase in brain IL-1 beta and fatigue that are associated with recovery from exercise-induced muscle damage. (C) 2010 Elsevier Inc. All rights reserved.