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Nociceptin/Orphanin FQ Suppresses Adaptive Immune Responses In Vivo and at Picomolar Levels In Vitro

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Abstract

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.

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The authors have no known conflicts of interest concerning the results reported in this manuscript.

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Authors and Affiliations

  1. Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Joseph J. Meissler, Martin W. Adler & Toby K. Eisenstein

  2. Department of Microbiology & Immunology, Temple University School of Medicine, 3400 North Broad St., Philadelphia, PA, 19140, USA

    Joseph J. Meissler, Toby K. Eisenstein & Toby K. Eisenstein

  3. Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Martin W. Adler

  4. Biostatistics Consulting Center, Department of Physiology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    John P. Gaughan

  5. Molecular Neurobiology and Addictive Neurochemistry Laboratory, National Institute of Psychiatry, Mexico City, Mexico

    Benito Anton, Phillipe Leff, Juan C. Calva, Rodolfo Acevedo, Alberto Salazar, Maura Matus & Anabel Flores

  6. Department of Physiology, National Institute of Cardiology, Mexico City, Mexico

    Martin Martinez

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  1. Benito Anton
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Correspondence to Toby K. Eisenstein.

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This work was supported by NIDA grants DA06650 and DA13429 and by SEP-CONACyT-2004-CO1-47804, UNAM MacroProject MP6-18, INPRFM-Subcuenta-100.

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Anton, B., Leff, P., Meissler, J.J. et al. Nociceptin/Orphanin FQ Suppresses Adaptive Immune Responses In Vivo and at Picomolar Levels In Vitro. J Neuroimmune Pharmacol 5, 143–154 (2010). https://doi.org/10.1007/s11481-010-9190-2

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