Dt. Lysle et al., MORPHINE-INDUCED ALTERATIONS OF IMMUNE STATUS - DOSE DEPENDENCY, COMPARTMENT SPECIFICITY AND ANTAGONISM BY NALTREXONE, The Journal of pharmacology and experimental therapeutics, 265(3), 1993, pp. 1071-1078
Although there is evidence to suggest that morphine can alter immune s
tatus, there is little information about the doses at which these effe
cts occur, the extent of the immune alterations and whether morphine's
immunomodulatory effects can be antagonized in a dose-dependent manne
r by an opioid antagonist. To address these issues, morphine (0, 5.0,
10.0, 15.0 or 25.0 mg/kg) was administered s.c. to Lewis rats. One hr
later, the spleen, mesenteric lymph nodes and a sample of peripheral b
lood were collected. Immune status was assessed by a variety of in vit
ro assays. For splenic lymphocytes, morphine induced a dose-dependent
suppression of lymphocyte function as measured by mitogen-induced prol
iferation, natural killer cell cytotoxicity, interleukin-2 production
and interferon production. For blood lymphocytes, the mitogen-induced
proliferative response was suppressed in a dose-dependent manner. In c
ontrast, morphine did not alter the capability of lymphocytes in the m
esenteric lymph nodes to proliferate or produce cytokines. In a separa
te study, naltrexone (0, 0.1, 1.0 or 10.0 mg/kg) was administered befo
re the injection of morphine (15 mg/kg). The results show that the imm
unomodulatory effects of morphine are antagonized by naltrexone. Colle
ctively, the results of this investigation show that morphine's immuno
modulatory effects are dose dependent, compartment specific and antago
nized by naltrexone.