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Neurohormonal modulation of natural resistance to a murine lymphoma
Abstract:
The hypothesis that neuroendocrine stimulation after aversive handling can alter natural resistance was examined in the tail electroshock (TES) model, a procedure that can activate pituitary neuropeptide secretion. Immediately after a brief TES session, the resistance of DBA/2J mice was suppressed in proportion to the intensity of the shock. Initial suppression of the natural resistance was rapidly reversed in longer treatment protocols, and repeated aversive stimulation augmented the antitumor response, leaving the mice more resistant to lymphoma than unhandled animals. Corticosterone was released into the serum after all acute handling procedures, and hydrocortisone inoculation suppressed antitumor responses. However, serum corticosterone levels did not quantitatively correlate with the alterations in natural resistance. The observation that TES-induced suppression of natural resistance could be reversed by the opiate receptor antagonist naltrexone suggested that endogenous opiated released after TES stimulation were immunosuppressive.
Insights
Aversive handling, like tail electroshock (TES), initially suppresses natural resistance but repeated stimulation enhances antitumor immunity in mice. This effect may involve endogenous opiates, not just corticosterone, suggesting a complex neuroendocrine influence on immune response.
Area of Science:
- Neuroimmunology
- Endocrinology
Background:
- The neuroendocrine system significantly influences immune responses.
- Aversive stimuli can activate neuroendocrine pathways, potentially altering natural resistance.
Purpose of the Study:
- To investigate if neuroendocrine stimulation from aversive handling modifies natural resistance.
- To explore the role of corticosterone and endogenous opiates in this process.
Main Methods:
- Utilized the tail electroshock (TES) model in DBA/2J mice.
- Assessed changes in natural resistance following acute and repeated TES.
- Measured serum corticosterone levels and used opiate receptor antagonists.
Main Results:
- Acute TES suppressed natural resistance dose-dependently.
- Repeated TES augmented antitumor responses, increasing resistance to lymphoma.
- Corticosterone release correlated with handling but not resistance changes.
- Opiate receptor antagonist naltrexone reversed TES-induced suppression.
Conclusions:
- Neuroendocrine stimulation via aversive handling can modulate natural resistance.
- Repeated aversive stimuli enhance antitumor immunity.
- Endogenous opiates, rather than corticosterone, appear to mediate the immunosuppressive effects of TES.