Unaccustomed muscular activity of even moderate intensity results in a certain amount of damage to contractile proteins and associated connective tissue. Eccentric exercise, in which muscles lengthen as they develop tension, is a natural part of most forms of exercise and is a particularly potent inducer of damage. An inflammatory response is associated with this muscle damage which might contribute to catabolic processes and may mediate muscle protein turn over responsible for repair. We propose to use eccentric exercise to examine age-related differences in the inflammatory response associated with muscle damage. The inflammatory response will be measured in blood and in skeletal muscle. Circulating immune complexes, functional complement activity, interleukin-l (IL-l), humor necrosis factor (TNF), and humoral cytotoxic factors will be measured. In muscle, HLA class I antigens, IL-l, and TNF concentrations and receptor numbers will be determined and the immunohistological characterization of invading leukocytes will be performed. The influence of the non- steroidal anti-inflammatory drug indomethacin, and the influence of dietary omega-3 fatty acid supplementation on all of these parameters will be assessed as well. By examining the systemic and intramuscular processes involved in damaging exercise, the mechanisms which may be critically important effectors of repair and peripheral training in young and old subjects will be characterized for the first time. This study will bring together novel methods to examine responses to muscle damage and differentiate between the young and the old. These data will be important for the athlete, but perhaps more important for the millions of old and young people beginning a program of increased physical activity. Moreover, the eccentric exercise protocol may prove to be a safe and controlled alternative experimental model for studying inflammation the elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR039595-03
Application #
3159770
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1989-03-01
Project End
1992-06-30
Budget Start
1991-03-01
Budget End
1992-06-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
St Pierre Schneider, B; Correia, L A; Cannon, J G (1999) Sex differences in leukocyte invasion in injured murine skeletal muscle. Res Nurs Health 22:243-50
Keller, H L; St Pierre Schneider, B; Eppihimer, L A et al. (1999) Association of IGF-I and IGF-II with myofiber regeneration in vivo. Muscle Nerve 22:347-54
Cannon, J G; St Pierre, B A (1997) Gender differences in host defense mechanisms. J Psychiatr Res 31:99-113
Cannon, J G; Fiatarone, M A; Meydani, M et al. (1995) Aging and dietary modulation of elastase and interleukin-1 beta secretion. Am J Physiol 268:R208-13
Cannon, J G (1995) Cytokines in aging and muscle homeostasis. J Gerontol A Biol Sci Med Sci 50 Spec No:120-3
Cannon, J G; Fiatarone, M A; Fielding, R A et al. (1994) Aging and stress-induced changes in complement activation and neutrophil mobilization. J Appl Physiol 76:2616-20
Wakabayashi, G; Cannon, J G; Gelfand, J A et al. (1994) Altered interleukin-1 and tumor necrosis factor production and secretion during pyrogenic tolerance to LPS in rabbits. Am J Physiol 267:R329-36
Lynch, E A; Dinarello, C A; Cannon, J G (1994) Gender differences in IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist secretion from mononuclear cells and urinary excretion. J Immunol 153:300-6
Dinarello, C A; Cannon, J G (1993) Cytokine measurements in septic shock. Ann Intern Med 119:853-4
Cannon, J G (1993) Exercise and resistance to infection. J Appl Physiol 74:973-81

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