Cellular mechanisms involved in morphine-mediated suppression of CTL activity

Based on a plethora of data from many laboratories, we have proposed the following mechanisms by which morphine alters immune homeostasis and immunocompetence in vivo (Fig. 2). Specifically, the administration of morphine subcutaneously via routing through blood interacts directly with opioid receptors on cells of the immune system or on receptors within the central nervous system. Although there is currently no evidence to support the direct involvement of morphine on lymphocyte opioid receptors, in vitro studies show the existence of functional, naloxone-sensitive opioid receptors (25). In addition, pharmacological and biochemical characterization of lymphocyte opioid receptors has been shown to be consistent in many instances, with the profile of neural-derived opioid receptors (25-27). Finally, recent molecular studies using oligonucleotide primers specific for the delta-class opioid receptor cloned from NG-108-15 cells (28) have been used in reverse transcription-polymerase chain reactions to generate a 400 bp product in SL which has 100% sequence homology with a published opioid receptor cloned from a brain library (35). However, future studies are necessary to establish the role of lymphocyte opioid receptors following the in vivo administration of opioids (e.g. fentanyl, methadone, and morphine). Since the administration of morphine subcutaneously appears to predominately interact with brain opioid receptors (3) located in the mesencephalon (5), other neuroendocrine systems become candidates for activation and subsequent direct modulation of immune function: (i) the HPA axis and (ii) the sympathetic nervous system (SNS).(ABSTRACT TRUNCATED AT 250 WORDS)