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Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon
Y Suzuki1, F K Conley, J S Remington
1Department of Immunology and Infectious Diseases, Palo Alto Medical Foundation, California 94301.
Abstract:
The effect of exogenous gamma interferon (IFN-gamma) on toxoplasmic encephalitis in a murine model was evaluated. The brains of CBA/Ca mice chronically infected with the ME49 strain of Toxoplasma gondii have a remarkable inflammatory cell infiltrate. Intravenous administration of six doses (5 x 10(5) U each) of recombinant IFN-gamma (rIFN-gamma) resulted in a remarkable decrease in numbers and foci of inflammatory cells in murine brain parenchyma and perivascular areas 1 day after the last injection of IFN-gamma. Immunoperoxidase staining revealed the presence of tachyzoites only on areas of acute focal inflammation, suggesting that the focal inflammation was caused by the proliferation of tachyzoites. The remarkable reduction in number of foci of acute focal inflammation in the brains of the IFN-gamma-treated mice indicates that the treatment resulted in diminished numbers of tachyzoites in the brains of the infected mice. The effect of rIFN-gamma was dose dependent; injection of 5 x 10(5) U every other day for a total of six doses was effective; injection of either 5 x 10(4), 5 x 10(3), or 5 x 10(2) U was not. This therapeutic effect of rIFN-gamma on encephalitis was not present 2 weeks after the last injection of rIFN-gamma. At that time, mice again had severe inflammation in their brains. Toxoplasma antibody production was not affected by treatment with rIFN-gamma. These results offer support for the value of injection of IFN-gamma in the treatment of toxoplasmic encephalitis in immunosuppressed patients, although its effect appears to be transient.
Insights
Recombinant interferon-gamma (IFN-gamma) significantly reduced inflammation and tachyzoites in murine brains during toxoplasmic encephalitis. However, this therapeutic effect was temporary, highlighting the need for sustained treatment strategies.
Area of Science:
- Immunology
- Neuroscience
- Infectious Diseases
Background:
- Toxoplasmic encephalitis, caused by Toxoplasma gondii, leads to significant brain inflammation.
- Chronic infection in mice models exhibits substantial inflammatory cell infiltration in brain tissues.
Purpose of the Study:
- To evaluate the therapeutic efficacy of exogenous gamma interferon (IFN-gamma) in a murine model of toxoplasmic encephalitis.
- To determine the dose-dependency and duration of the therapeutic effect of recombinant IFN-gamma (rIFN-gamma).
Main Methods:
- CBA/Ca mice chronically infected with Toxoplasma gondii (ME49 strain) were treated with varying doses of rIFN-gamma intravenously.
- Brain tissues were analyzed for inflammatory cell infiltrates and tachyzoite presence using immunoperoxidase staining.
- Toxoplasma antibody production was assessed to evaluate the systemic immune response.
Main Results:
- A significant reduction in inflammatory cell numbers and foci was observed in the brains of mice treated with high-dose rIFN-gamma (5 x 10(5) U).
- The reduction in inflammation correlated with diminished tachyzoite numbers, suggesting an anti-parasitic effect.
- The therapeutic effect was dose-dependent and transient, with inflammation returning two weeks after treatment cessation.
Conclusions:
- Recombinant IFN-gamma demonstrates a transient therapeutic effect on toxoplasmic encephalitis in mice by reducing parasite load and inflammation.
- Sustained or repeated administration may be necessary for long-term management of toxoplasmic encephalitis.
- These findings support the potential use of IFN-gamma in treating immunosuppressed patients, with consideration for its temporary efficacy.