IMMUNE-SYSTEM ACTIVATION AND FATIGUE DURING TREADMILL RUNNING - ROLE OF INTERFERON

Extreme fatigue often accompanies infection and other diseases, but th e causal mechanisms are unknown. Recent research has focused on Variou s cytokines as potential immune system mediators of fatigue during ill ness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most in terest in this regard. Purpose: The purpose of this research was to st udy the effect of IFN-odp on fatigue during treadmill running in mice. Methods: Mice (male CD-I) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were inj ected 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 (similar to 3 h, 19-24 m.min(-1), 5% g rade, no shock). In experiment 2 (EXP 2), mice were injected 24 h befo re exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-a lpha/beta antibody (pl:C + Ab). Results: The results of EXP I showed t hat the plasma IFN-alpha/beta liter was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was s ignificantly reduced only when the exercise occurred 24 h after inject ion (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta an tibody attenuated both the pI:C-induced increase in plasma IFN-alpha/b eta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001). Conclusions: These results suggest that immune system activa tion by pI:C was associated with early fatigue during prolonged treadm ill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.