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Enkephalinase-inhibitors modulate immune responses.
B D Janković1, J Veljić, G Pesić
1Immunology Research Center, Belgrade, Yugoslavia.
The International Journal of Neuroscience
|July 1, 1991
Summary
Endogenous opioids, particularly enkephalins, influence immune responses. This study found that inhibiting specific peptidases with drugs like bestatin and actinonin modulated immune cell activity and antibody production in rats, suggesting a key role for these natural compounds in immunity.
Area of Science:
- Immunology
- Neuroendocrinology
- Pharmacology
Background:
- Exogenous opioid peptides, especially enkephalins, are known to modulate immune functions both in vivo and in vitro.
- The role of endogenous opioids in regulating immune responses remains an area of active investigation.
- Peptidase inhibitors offer a pharmacological tool to probe the activity of endogenous opioid systems.
Purpose of the Study:
- To investigate the immunomodulatory effects of endogenous opioids by administering peptidase inhibitors centrally and peripherally in rats.
- To explore the dose-dependent effects of specific enkephalin-related peptidase inhibitors on humoral immune responses.
Main Methods:
- Rats sensitized with sheep red blood cells (SRBC) were treated with four peptidase inhibitors (bestatin, (Des-Tyr1)Met-Enk, actinonin, (N-C)Phe-Leu) via intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration.
- Animals received varying doses of inhibitors or saline as a control.
- Humoral immune responses, specifically plaque-forming cell (PFC) response and hemagglutinin production, were measured.
Main Results:
- Intraperitoneal administration of bestatin and (N-C)Phe-Leu at lower doses (0.2 mg/kg) potentiated PFC response and hemagglutinin production, while higher doses (1 mg/kg) suppressed these responses.
- Actinonin and (Des-Tyr1)Met-Enk administered i.p. at both tested doses (0.2 and 1 mg/kg) potentiated humoral immune responses.
- Central (i.c.v.) administration of all inhibitors showed dose-dependent immunomodulatory effects: lower doses (0.005–0.02 mg/kg) increased immune responses, whereas higher doses (0.2–0.5 mg/kg) decreased them.
Conclusions:
- The findings suggest that endogenous enkephalins play a significant role in immune mechanisms.
- Peptidase inhibitors targeting endogenous enkephalin pathways can exert dose-dependent immunomodulatory effects, both peripherally and centrally.
- This study provides evidence for the intricate connection between the endogenous opioid system and immune regulation.