Search

Neuromediators such as dopamine (DA), serotonin (5-HT) and neuroopioids are known to be involved in the immune response control. This review has summarized the evidence supporting roles for brain DA (D(1), D(2)), 5-HT (5-HT(1A), 5-HT(2A)) and opioid (mu, delta, kappa) receptor subtypes in regulating immune function. Activation of postsynaptic D(1)- and D(2)-receptors produced immunostimulation while their blockade or activation of presynaptic D(2)-receptors mediated an immunoinhibitory effect. Activation of mu- and delta(1)-opioid receptors also increased the immune reaction intensity. Activation of postsynaptic 5-HT(1A)-, 5-HT(2A)-receptors, delta(2)- and kappa-opioid receptors resulted in immunosuppression while the blockade of postsynaptic 5-HT(1A)-, 5-HT(2A)-receptors or activation of somatodendritic 5-HT(1A)-autoreceptors resulted in the immune response stimulation. Immunomodulating effects of drugs acting at various mediator and opioid receptor subtypes depend on the initial psychoemotional state of animals (aggression, submission, depression). The presented data may have implications for the treatment of emotional stress and mental disorders associated with changes in activity of brain DA, 5-HT, opioid systems and their receptor function as well as immune reactivity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Orphanin FQ/nociceptin (OFQ/N) has been shown to modulate nociception, responses to stress and anxiety. We investigated OFQ/N function in human immune cells. We find that monocytic U937, T lymphocytic CEM, and MOLT-4 cell lines express OFQ/N binding sites at levels comparable to that of human SH-SY5Y neuroblastoma cells. We show that OFQ/N receptors are functionally coupled to G proteins in these cells. Finally OFQ/N decreases proliferation of phytohemagglutinin-stimulated peripheral blood mononuclear cells in vitro at doses ranging from 10(-13) to 10(-8) M. Thus, our data suggest that OFQ/N and OFQ/N receptor may act as an immunomodulatory system.

To investigate the significance of endogenous, neuroleptic-like gamma-type endorphins and their putative receptors, polyclonal and monoclonal antibodies against gamma-type endorphins, which may bio-inactivate the ligands for the receptors, and monoclonal anti-idiotype antibodies, which presumably bind to the receptors, were injected into the nucleus accumbens of the rat brain. The desenkephalin-gamma-endorphin-induced antagonism of the hypomotility response elicited by challenge with apomorphine injected into the nucleus accumbens was used as test system. Both the anti-desenkephalin-gamma-endorphin antibodies and anti-idiotype antibodies blocked the action of exogenous desenkephalin-gamma-endorphin. Thus, the anti-idiotype antibodies may serve as receptor antagonists. Chronic treatment (injection into the nucleus accumbens) with the anti-idiotype antibodies induced sustained hypermotility, decreased habituation and impaired passive avoidance behavior. In such treated animals local treatment with apomorphine did not elicit hypomotility. It is suggested that gamma-type endorphins influence the setpoint for feedback regulation in dopaminergic neurons equipped with gamma-type endorphin receptor systems.

Antibodies that specifically recognize and bind opiate receptors were developed by the anti-idiotypic method. Antimorphine antibodies were generated in rabbits and showed selective binding to various opiate ligands. Guinea pigs were immunized with antimorphine antibodies to produce anti-idiotypic antibodies that cross-reacted with opiate receptors. Guinea pig antiserum inhibited binding of naloxone (0.6 nmol) to mouse brain homogenate. In isolated mouse vas deferens, contraction of electrically stimulated tissue was inhibited by the antiserum. The results indicate that anti-idiotypic antibodies which interact with opiate receptors were developed without isolating receptors.