Immunosuppression by a novel analgesic-opioid agonist.
The effect of a new, centrally acting analgesic, 2-n-pentyloxy-2-phenyl-4- methyl-morpholine (PM) on the humoral antibody isotype responses, mitogenic responses, and interleukin production and assay was studied. Treatment with this opioid agonist exerted a suppressive effect on the antibody responses to TD [sheep red blood cells (SRBC), fluoresceinated human gamma globulin (HGG-FITC)] and TI [fluoresceinated dextran (DEX-FITC), lipopolysaccharide (LPS)]antigens in mice. The suppression was found to be dose- and time-dependent for all antigens tested, suggesting that PM affected both T and B cells. PM impaired lymphocyte functions, as the in vitro T and B mitogen reactions were inhibited in a dose- and time-dependent manner in mice and rats. PM, even at the highest concentration used, could not completely inhibit the production of interleukin 1 (IL-1)-like activity, but it caused complete inhibition, in a dose-dependent manner, of the production of IL-2-like activity. In addition, PM inhibited the assays of both IL-1 and IL-2. Naloxone counteracted all immunosuppressive effects of PM in vivo and in vitro. From this it was concluded that PM operates on the immune system directly, via opioid receptor mechanisms. Our data suggest that immunosuppression by PM, an opioid agonist, may be exerted by an inhibition of interleukin action on lymphocytes, and they confirm the important role of opiate receptors in lymphocyte function.
Hadjipetrou-Kourounakis
L
L
Department of Biology, School of Science, Aristotelian University, Thessaloniki, Greece.
Karagounis
E
E
Rekka
E
E
Kourounakis
P
P
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects; D000955:Antigens, T-Independent / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D006241:Haptens / Q000276:immunology; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000008:administration & dosage*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013861:Thiocyanates
D000955:Antigens, T-Independent; D005452:Fluoresceins; D006241:Haptens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D007376:Interleukin-2; D009025:Morpholines; D013861:Thiocyanates; C059601:2-n-pentyloxy-2-phenyl-4-methylmorpholine; D009270:Naloxone; D016650:Fluorescein-5-isothiocyanate