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 BAF 1/J mice. Twenty-four hours after pump implantation, mice were challenged with sub-optimal, optimal or supraoptimal immunnizing 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 supressive 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 and provide evidence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response.