THE IN-VIVO EFFECTS OF OPIOID-PEPTIDES ON THE MURINE IMMUNE-RESPONSE

We have previously reported that met-enkephalin has dual immunomodulat ory properties in vitro. We have continued this investigation using an in vivo system: In this study, Alzet miniosmotic pumps were loaded wi th either met-enkephalin, DTLET or FK 33-824 and were surgically impla nted into BAF/J mice. Twenty-four hours after pump implantation, mice were challenged with:sub-optimal, optimal or supraoptimal immunizing d oses of antigen. The immune response was assessed 4 or 5 days after pr imary immunization. FK 33-824, a met-enkephalin analogue, had no effec t on the response of mice challenged with a suboptimal antigen dose. H owever, FK 33-824, at a pump concentration of 10(-3) M, suppressed the response against optimal challenge doses of antigen. At a pump concen tration of 10(-8) M, FK 33-824 suppressed, enhanced or had no effect o n the supraoptimal antigen dose-induced immune response. The suppressi ve effect of FK 33-824 in mice immunized with either optimal or suprao ptimal doses of antigen was blocked by naloxone: Met-enkephalin and it s delta opioid receptor specific analogue, DTLET, had no effect on the immune response to optimal antigen immunization. These results indica te that FK 33-824 has in vivo immunomodulatory activity and provide ev idence that opioid peptides may either upregulate or downregulate the in vivo immune response depending on the strength of the response.