This is a research project with three specific aims. Using a murine model, the first aim is to study the relationship between cytokine levels in serum, spleen and brain and the development of fatigue.The second is to attempt to determine whether the administration of neutralizing antibodies specific to cytokines blocks the development of fatigue. Lastly, the author will evaluate the modulating effects of age, sex and genetics on the development and severity of chronic fatigue. Two objective measures will be used to quantify fatigue: loss of daily running activity on an exercise wheel and time elapsed before resumption of grooming behavior after swimming (exercise-induced fatigue). Corynebacterium parvum antigen will be used to stimulate the immune system in BALB/c mice. Cytokine levels in serum will be correlated with development of fatigue. Antibodies specific to these cytokines will be used to determine the involvement of cytokines in inducing fatigue. The influence of age, sex and genetic factors on the degree and duration of fatigue will be explored.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI035110-02
Application #
2070525
Study Section
Special Emphasis Panel (CFS (S1))
Project Start
1994-08-01
Project End
1997-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Minneapolis Medical Research Fdn, Inc.
Department
Type
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55415
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Sheng, W S; Hu, S; Lamkin, A et al. (1996) Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice. Clin Immunol Immunopathol 81:161-7
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Chao, C C; Hu, S; Sheng, W S et al. (1995) Tumor necrosis factor-alpha mediates the release of bioactive transforming growth factor-beta in murine microglial cell cultures. Clin Immunol Immunopathol 77:358-65
Hu, S; Sheng, W S; Peterson, P K et al. (1995) Cytokine modulation of murine microglial cell superoxide production. Glia 13:45-50
Chao, C C; Hu, S; Peterson, P K (1995) Glia, cytokines, and neurotoxicity. Crit Rev Neurobiol 9:189-205
Anderson, W R; Martella, A; Drake, Z M et al. (1995) Correlative transmission and scanning electron microscopy study of microglia activated by interferon-gamma and tumor necrosis factor-alpha in vitro. Pathol Res Pract 191:1016-22