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Lethality of morphine in mice infected with Toxoplasma gondii
C C Chao1, B M Sharp, C Pomeroy
1Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Abstract:
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.
Insights
Morphine addiction significantly increases mortality in mice infected with Toxoplasma gondii. This effect, mediated by opiate receptors, is linked to the host immune response during infection.
Area of Science:
- Immunology
- Pharmacology
- Infectious Diseases
Background:
- Opiates are known to modulate immune system functions.
- The impact of morphine on acute Toxoplasma gondii infection pathogenesis remains unclear.
Purpose of the Study:
- To investigate the effect of morphine on the pathogenesis of acute Toxoplasma gondii infection in a murine model.
Main Methods:
- Mice were subjected to repeated or single morphine sulfate injections.
- Mortality rates were assessed in infected and non-infected mice.
- Naltrexone and sulfadiazine were used to investigate the mechanisms of morphine-induced mortality.
Main Results:
- Repeated morphine administration led to 86% mortality in infected mice, compared to 0% in controls.
- A single morphine dose at day 13 postinfection increased mortality to 94%.
- The lethal effect was blocked by naltrexone and sulfadiazine, indicating opiate receptor involvement and an active infectious state.
Conclusions:
- Immune activation during Toxoplasma gondii infection plays a critical role in morphine-induced mortality.
- Opiate receptor mechanisms are involved in this heightened susceptibility.
- The findings highlight the complex interplay between opioid use, immune response, and parasitic infection.