Both T cells and macrophages are targets of kappa-opioid-induced immunosuppression.
We have previously shown that antibody responses are inhibited following administration of kappa-opioid agonists. We found that the inhibition was blocked by either naloxone or the kappa-selective antagonist norbinaltorphimine. This inhibitory activity is apparent after short-term treatment with the kappa-opioid agonist. In an attempt to identify the cell populations which serve as the target for this immunosuppressive effect, we have carried out cell fractionation analyses to generate isolated T cells and macrophages. Using multiple cell fractionation methods, we have determined that short-term treatment of either T cells or macrophages with the kappa-opioid agonist U50,488H results in significant inhibition of in vitro antibody responses. We also find that the inhibition of both T cell and macrophage activity can be blocked by naloxone. These studies demonstrate that resting T cells and macrophages express kappa-opioid receptors and exhibit significant opioid responsiveness prior to activation by antigen.
Guan
L
L
Department of Microbiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Townsend
R
R
Eisenstein
T K
TK
Adler
M W
MW
Rogers
T J
TJ
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D003864:Depression, Chemical; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D015213:Neuroimmunomodulation; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012397:Rosette Formation; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects*
D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer