Immune system activation and fatigue during treadmill running: role of interferon

Extreme fatigue often accompanies infection and other diseases, but the causal mechanisms are unknown. Recent research has focused on various cytokines as potential immune system mediators of fatigue during illness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard.

The purpose of this research was to study the effect of IFN-alpha/beta on fatigue during treadmill running in mice.

Mice (male CD-1) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1 body weight) or saline (CON) 12 or 24 h before the exercise session. These sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24 m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-alpha/beta antibody (pI:C + Ab).

The results of EXP 1 showed that the plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was significantly reduced only when the exercise occurred 24 h after injection (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C-induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001).

These results suggest that immune system activation by pI:C was associated with early fatigue during prolonged treadmill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.