Lethality of morphine in mice infected with Toxoplasma gondii.
Opiates modulate a variety of immune responses. We investigated the effect of morphine on the pathogenesis of an acute Toxoplasma gondii infection. Repeated s.c. injections with morphine sulfate (300 mg/kg) every 36 hr addicted mice and increased markedly the mortality of mice infected with an avirulent strain of T. gondii (86%) vs. 0% mortality in addicted and control mice, respectively, P less than .001). However, a single challenge with morphine (300 mg/kg) also markedly (P less than .001) increased mortality (94%) of infected mice when the morphine was administered at day 13 postinfection; susceptibility to the lethal effect was not observed until day 9 postinfection, a time when immune reactivity was evident (i.e., 3- to 4-fold splenic enlargement). This lethal effect was attenuated by pretreatment with naltrexone, suggesting involvement of an opiate receptor mechanism. Sulfadiazine treatment abrogated morphine-induced mortality, indicating a prerequisite of an active infectious state. These findings suggest that immune activation by T. gondii infection plays a critical role in morphine-induced mortality in this murine model.
Chao
C C
CC
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Sharp
B M
BM
Pomeroy
C
C
Filice
G A
GA
Peterson
P K
PK
D000818:Animals; D004361:Drug Tolerance; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000633:toxicity*; D011425:Propionibacterium acnes / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D009020:Morphine