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Tolerance to appetite suppression induced by peptidoglycan
K J Biberstine1, D S Darr, R S Rosenthal
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202, USA.
Infection and Immunity
|September 1, 1996
Summary
Repeated exposure to peptidoglycan (PG) fragments causes rats to develop tolerance to appetite suppression. This tolerance is initially nonspecific but later becomes specific to PG, linked to antibody production.
Area of Science:
- Immunology
- Microbiology
- Physiology
Background:
- Peptidoglycan (PG) fragments from Neisseria gonorrhoeae can suppress appetite and body weight gain in rats.
- Soluble PG fragments are hypothesized to contribute to appetite loss during bacterial infections.
Purpose of the Study:
- To investigate the effects of repeated daily injections of PG fragments on appetite in rats.
- To explore the mechanisms of tolerance to PG-induced appetite suppression.
Main Methods:
- Male Lewis rats received daily intraperitoneal injections of purified, soluble, O-acetylated PG fragments (S-O-PG).
- Food consumption and body weight were monitored.
- Tolerance to S-O-PG and other agents (LPS, muramyl dipeptide, interleukin-1) was assessed at different time points.
- Anti-PG antibody activity was measured using an enzyme-linked immunosorbent assay.
Main Results:
- Initial S-O-PG injection suppressed food consumption by ~35%.
- Repeated daily S-O-PG injections led to tolerance (nonresponsiveness) to appetite suppression by day four.
- Rats developed cross-tolerance to LPS, muramyl dipeptide, and interleukin-1 early on.
- A late tolerance specific to S-O-PG emerged after 30 days, associated with increased anti-PG antibody levels.
Conclusions:
- Repeated administration of PG fragments induces tolerance to their appetite-suppressing effects.
- Two distinct mechanisms of tolerance exist: early nonspecific tolerance and late PG-specific tolerance.
- Late tolerance is associated with the development of specific antibodies against PG.