Nociceptin/orphanin FQ suppresses adaptive immune responses in vivo and at picomolar levels in vitro.
Nociceptin/orphanin FQ (N/OFQ), added in vitro to murine spleen cells in the picomolar range, suppressed antibody formation to sheep red blood cells in a primary and a secondary plaque-forming cell assay. The activity of the peptide was maximal at 10(-12) M, with an asymmetric U-shaped dose-response curve that extended activity to 10(-14) M. Suppression was not blocked by pretreatment with naloxone. Specificity of the suppressive response was shown using affinity-purified rabbit antibodies against two N/OFQ peptides and with a pharmacological antagonist. Antisera against both peptides were active, in a dose-related manner, in neutralizing N/OFQ-mediated immunosuppression, when the peptide was used at concentrations from 10(-12.3) to 10(-11.6) M. In addition, nociceptin given in vivo by osmotic pump for 48 h suppressed the capacity of spleen cells placed ex vivo to make an anti-sheep red blood cell response. These studies show that nociceptin directly inhibits an adaptive immune response, i.e., antibody formation, both in vitro and in vivo.
Anton
Benito
B
Molecular Neurobiology and Addictive Neurochemistry Laboratory, National Institute of Psychiatry, Mexico City, Mexico.
Leff
Phillipe
P
Meissler
Joseph J
JJ
Calva
Juan C
JC
Acevedo
Rodolfo
R
Salazar
Alberto
A
Matus
Maura
M
Flores
Anabel
A
Martinez
Martin
M
Adler
Martin W
MW
Gaughan
John P
JP
Eisenstein
Toby K
TK
D056704:Adaptive Immunity / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D055104:Infusions, Subcutaneous; D051379:Mice; D008809:Mice, Inbred C3H; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D000097629:Nociceptin
D007106:Immune Sera; D007166:Immunosuppressive Agents; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D000097629:Nociceptin