title: The in vivo effects of opioid peptides on the murine immune response.
abstract: We have previously reported that met-enkephalin has dual immunomodulatory properties in vitro. We have continued this investigation using an in vivo system. In this study, Alzet miniosmotic pumps were loaded with either met-enkephalin, DTLET or FK 33-824 and were surgically implanted into BAF1/J mice. Twenty-four hours after pump implantation, mice were challenged with sub-optimal, optimal or supraoptimal immunizing doses of antigen. The immune response was assessed 4 or 5 days after primary immunization. FK 33-824, a met-enkephalin analogue, had no effect on the response of mice challenged with a suboptimal antigen dose. However, FK 33-824, at a pump concentration of 10(-3) M, suppressed the response against optimal challenge doses of antigen. At a pump concentration of 10(-8) M, FK 33-824 suppressed, enhanced or had no effect on the supraoptimal antigen dose-induced immune response. The suppressive effect of FK 33-824 in mice immunized with either optimal or supraoptimal doses of antigen was blocked by naloxone. Met-enkephalin and its delta opioid receptor specific analogue, DTLET, had no effect on the immune response to optimal antigen immunization. These results indicate that FK 33-824 has in vivo immunomodulatory activity and provide evidence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response.
authors.affiliation: Department of Microbiology, University of New Mexico School of Medicine, Albuquerque.
authors.forename: R U
authors.initials: RU
authors.lastname: Chukwuocha
authors.forename: E
authors.initials: E
authors.lastname: Reyes
authors.forename: S
authors.initials: S
authors.lastname: Tokuda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D005260:Female; D007114:Immunization; D007159:Immunologic Tests; D015918:Infusion Pumps, Implantable; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*
chemical_list: D009842:Oligopeptides; D011957:Receptors, Opioid; D004744:Enkephalin, Methionine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C037653:deltakephalin; D003345:Corticosterone