In preliminary experiments we have found that intraperitoneal administration of the antibiotic polymyxin to rats resulted in a marked decrease in the night-time rise in body temperature. ORal administration of the antibiotics bacitracin and streptomycin reduced both the night-time and day-time body temperature of rats. Gerfree mice have a significant decrease in the magnitude of the night-time rise in body teomperature, compared to conventionally-reared mice. Based on these data, we hypothesize that the absolute body temperature and the daily rhythm in body temperature are in part attributable to endotoxin or other bacterial products originating in the gastrointestinal tract. Studies are outlined in which we will determine whether administration of normal mouse intestinal flora to germfree mice restores the amplitude in their body temperature rhythm; in additon, experiments are outlined to determine the origin of these signals (e.g. form endotoxin, form Gram-positive organism, etc.). Other studies are designed to determine whether the C3H/HeJ mouse (the endotoxin-resistant mouse) has an attenuation in its rhythm in body temperature compared to the C3H/OuJ mouse. In endotoxin or some other bacterial product form the gut afects the rhythm in body temperature, it may be doing so via the protein mediator of fever and other """"""""acute-phase responses,"""""""" interleukin-1 (IL-1). A series of experiments are outlined to test the hypothesis that IL-1 may vary on a circadian basis, and that this rhythm in IL-1 influences th erhythm in body temperature. It is possible that the host requires some signal (s?) form the intestinal flora for what most believe are """"""""endogenous"""""""" set-points (such as temperature), and rhythms in these set-points. Were this the case, then our view towards the commensal relationship that clearly exists between ourselves and our gut flora would be markedly altered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038984-03
Application #
3238618
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1987-09-01
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Conn, C A; Franklin, B; Freter, R et al. (1991) Role of gram-negative and gram-positive gastrointestinal flora in temperature regulation of mice. Am J Physiol 261:R1358-63
LeMay, L G; Vander, A J; Kluger, M J (1990) Role of interleukin 6 in fever in rats. Am J Physiol 258:R798-803
Kluger, M J; Conn, C A; Franklin, B et al. (1990) Effect of gastrointestinal flora on body temperature of rats and mice. Am J Physiol 258:R552-7
LeMay, L G; Vander, A J; Kluger, M J (1990) The effects of psychological stress on plasma interleukin-6 activity in rats. Physiol Behav 47:957-61
Mrosovsky, N; Molony, L A; Conn, C A et al. (1989) Anorexic effects of interleukin 1 in the rat. Am J Physiol 257:R1315-21