Enhanced humoral response in kappa-opioid receptor knockout mice.
Opiates are major analgesics and addictive drugs described also as immunomodulators. Here, we investigated the contribution of kappa-opioid receptor (KOR) activity in immunity in vivo by studying immune responses in KOR knockout mice. These animals displayed a modest reduction in thymus cellularity and CD4(+) cell ratio, parallel to a slight increase in immature CD4(+)CD8(+) lymphocytes. In spleen, KOR null animals showed augmented cell number with no change in cell distribution. T and B lymphocyte proliferative capabilities in vitro, Natural Killer activity and steady-state Ig levels were unchanged in KOR-/- mice. We immunized the mice with the antigen keyhole limpet hemocyanin (KLH). Compared to wild-type (WT) mice, KOR-/- animals produced significant higher levels of antigen-specific total Ig, IgM, IgG1 and IgG2a antibodies. This enhancement of humoral activity was not observed in mu-opioid receptor and delta-opioid receptor knockout animals. These results show that endogenous activation of kappa-opioid receptors may exert a tonic inhibition of antibody (Ab) response.
Gavériaux-Ruff
Claire
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP10142, 67404 Illkirch Cedex, C.U. de Strasbourg, France. gaveriau@igbmc.u-strasbg.fr
Simonin
Frédéric
F
Filliol
Dominique
D
Kieffer
Brigitte L
BL
D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology / Q000494:pharmacology; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D015213:Neuroimmunomodulation / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D017473:Receptors, Opioid, kappa; D003208:Concanavalin A