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Low dosages of interleukin 1 protect mice against lethal cerebral malaria
J H Curfs1, J W van der Meer, R W Sauerwein
1Department of Medical Microbiology, Faculty of Medicine, Catholic University of Nijmegen, The Netherlands.
Abstract:
In cerebral malaria, pathological changes can be found in the brain of infected people and in the brain of Plasmodium berghei-infected mice. The pathogenesis of cerebral malaria in mice is believed to be due to an immunopathological reaction giving rise to an excessive production of cytokines such as interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). We find that low doses of interleukin 1 (IL-1) protect mice against cerebral malaria; IL-1 also inhibits parasitemia. The IL-1 effect on parasitemia was not observed in nude mice and was at least partly reversed in mice treated with IL-1 in combination with antibody to IFN-gamma, indicating the involvement of T cells. Mice protected against development of cerebral malaria by IL-1 treatment developed the syndrome when TNF was given as observed in control infected mice or infected mice treated with inactivated IL-1.
Insights
Low doses of interleukin-1 (IL-1) protect mice from cerebral malaria by inhibiting T cell-mediated immunopathology. This finding offers potential therapeutic insights for managing severe malaria complications.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- Cerebral malaria involves brain pathology in humans and Plasmodium berghei-infected mice.
- Pathogenesis is linked to an overactive immune response with high levels of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF).
Purpose of the Study:
- To investigate the protective role of interleukin-1 (IL-1) in murine cerebral malaria.
- To elucidate the immunological mechanisms underlying IL-1's effects.
Main Methods:
- Administration of low-dose IL-1 to Plasmodium berghei-infected mice.
- Assessment of cerebral malaria development and parasitemia.
- Evaluation of IL-1 effects in nude mice and in combination with anti-IFN-gamma antibodies.
- Testing the impact of TNF administration on IL-1-protected mice.
Main Results:
- Low-dose IL-1 significantly protected mice against cerebral malaria and reduced parasitemia.
- IL-1's protective effect on parasitemia was dependent on T cells, as shown in nude mice and with IFN-gamma blockade.
- IL-1-protected mice developed cerebral malaria when administered TNF, similar to control groups.
Conclusions:
- Interleukin-1 (IL-1) demonstrates a protective effect against cerebral malaria in a murine model.
- The protective mechanism involves modulation of T cell-dependent immunopathology and cytokine production, particularly IFN-gamma.
- IL-1 may represent a potential therapeutic agent for cerebral malaria, warranting further investigation into its immunomodulatory functions.