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Is the endogenous antipyretic neuropeptide alpha-MSH responsible for reduced fever in aged rabbits?
1Physiology Department, University of Texas Health Science Center at Dallas 75235.
Abstract:
The reduced febrile response in aged man has been noted since the beginning of clinical thermometry. Our previous research on aged rabbits and squirrel monkeys disclosed a similar reduced fever, presumably due to a decrease in central receptors for endogenous pyrogen. However, because central alpha-melanocyte stimulating hormone (MSH) appears to have a potent role in physiological control of fever, it may be that increased release of the peptide is responsible for the reduced febrile response in aged animals. To test this idea, antiserum specific to MSH was administered intracerebroventricularly to rabbits of known age. The antiserum given according to three schedules of treatment augmented fever caused by IV injections of interleukin-1 (IL-1) in young (less than 2 years) male and female rabbits. Aged female rabbits (3-5+ years) and females aged 2-3 years showed significant augmentation of fever only after pretreatment plus acute injection of antiserum. A single ICV injection of MSH (200 ng) reduced fever in all groups with the greatest antipyretic effect in the aged females. The results indicate that while aged rabbits have an increased antipyretic response to central MSH, binding of the endogenous peptide does not result in marked increases in fever in these animals. Thus, whereas a change in central MSH sensitivity may contribute to reduced fever in aged homeotherms, a reduction in central pyrogen receptors appears to be the most parsimonious explanation.
Insights
Aging reduces fever response in animals. Studies show central alpha-melanocyte stimulating hormone (MSH) may play a role, but reduced pyrogen receptors are the most likely cause of diminished fever in aged homeotherms.
Area of Science:
- Neuroscience
- Immunology
- Gerontology
Background:
- Reduced febrile response in aged individuals is a long-observed phenomenon.
- Previous studies indicated decreased central pyrogen receptors in aged animals.
- Central alpha-melanocyte stimulating hormone (MSH) is implicated in fever regulation.
Purpose of the Study:
- To investigate the role of central alpha-melanocyte stimulating hormone (MSH) in the reduced fever response of aged rabbits.
- To determine if increased MSH release contributes to diminished fever in aging.
Main Methods:
- Administration of MSH-specific antiserum intracerebroventricularly in rabbits of varying ages.
- Induction of fever using interleukin-1 (IL-1) injections.
- Assessment of fever augmentation or reduction following antiserum or MSH administration.
Main Results:
- MSH antiserum augmented IL-1-induced fever in young rabbits and some aged female rabbits.
- A single MSH injection reduced fever in all groups, with a greater effect in aged females.
- Aged rabbits showed increased antipyretic response to central MSH but not increased fever upon binding.
Conclusions:
- While altered central MSH sensitivity may contribute to reduced fever in aging, it's not the sole factor.
- A decrease in central pyrogen receptors remains the most plausible explanation for reduced fever in aged homeotherms.
- This research clarifies the complex interplay between MSH, pyrogens, and fever regulation in aging.