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The Response Of Voluntary Physical Activity To R-848 Via Tlr7 In Mice


Board #100 June 4 8:00 AM - 9:30 AM

Yano, Hiromi, FACSM1; Woods, Jeffrey A., FACSM2

Medicine & Science in Sports & Exercise: May 2010 - Volume 42 - Issue 5 - p 645
doi: 10.1249/01.MSS.0000385798.94025.6c
E-29 Free Communication/Poster - Immunology II: JUNE 4, 2010 7:30 AM - 12:30 PM: ROOM: Hall C

1Kawasaki Univ. Med Welfare, Kurashiki, Japan. 2University of Illinois at Urbana-Champaign, Urbana, IL.


(No disclosure reported)

One characteristic of sickness behavior in mice is demonstrated by a reduction in voluntary wheel-running activity during infection. Single-stranded (ss) RNAs, which are nucleic acids in many RNA virus, activates to produce pro-inflammatory cytokine, type I interferon and prostanoid via toll-like receptor (TLR)7. However, how voluntary wheel-running activity is regulated after ssRNA treatment is unknown.

PURPOSE: To determine whether ssRNA-induced TNF-a, IFN-a and/or PGE2 production is responsible for reduced spontaneous physical activity, we measured R-848, which is TLR7 agonist, -induced changes in voluntary wheel-running activity in mice.

METHODS: Male C3H/HeN mice were injected with R-848 (0, 1, and 5 mg/kg i.v.) and then were measured their wheel-running activity. Also to clarify the effect of R-848-induced TNF-a, IFN-a and PGE2 on wheel-running behavior, we treated with those inhibitors such as pentoxifylline (PF), anti-IFN-a antibody and indomethacin (IDM), respectively, before or after R-848 injection.

RESULTS: R-848 treatment dose-dependently reduced the wheel-running activity, and the treatment induced an increase in plasma TNF-a, IFN-a and PGE2 concentration. However the wheel-running activity was not attenuated by PF, the neutralizing antibody specific to IFN-a, and IDM treatment.

CONCLUSIONS: Our results suggest that the transient reduction in physical activity after R-848 injection is induced dose dependently, and that the mediator might not be R848-induced TNF-a, IFN-a and PGE2.

© 2010 American College of Sports Medicine