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Published on: January 2, 2013
Interleukin-10 modulates susceptibility in experimental cerebral malaria
S Kossodo1, C Monso, P Juillard
1Department of Anaesthesiology, University of Geneva, Switzerland.
Abstract:
In this study, we examined the effects of interleukin-10 (IL-10) on the outcome of experimental cerebral malaria (CM), a lethal neurological syndrome that occurs in susceptible strains of mice after infection with Plasmodium berghei ANKA (PbA). Constitutive IL-10 mRNA levels were significantly higher in the spleen and brain of resistant animals. In vivo neutralization of endogenous IL-10 in CM-resistant mice induced the neurological syndrome in 35.7% of these mice, as opposed to 7.7% in controls. IL-10 inhibited PbA antigen-specific interferon-gamma (IFN-gamma) production in vitro but not tumour necrosis factor (TNF) serum levels in vivo. Susceptible mice, on the other hand, were significantly protected against CM when injected with recombinant IL-10. Overall, our findings suggest that IL-10 plays a protective role against experimental cerebral malaria.
Insights
Interleukin-10 (IL-10) protects against experimental cerebral malaria (CM). Blocking IL-10 in resistant mice induced CM, while giving IL-10 to susceptible mice prevented it, highlighting IL-10's protective role.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- Experimental cerebral malaria (CM) is a lethal neurological condition.
- Plasmodium berghei ANKA (PbA) infection causes CM in susceptible mice.
- The role of interleukin-10 (IL-10) in CM pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the impact of IL-10 on the outcome of experimental cerebral malaria (CM).
- To determine if IL-10 has a protective or detrimental effect in CM.
Main Methods:
- Measured IL-10 mRNA levels in spleen and brain of resistant and susceptible mice infected with PbA.
- Neutralized endogenous IL-10 in CM-resistant mice using in vivo antibody blockade.
- Administered recombinant IL-10 to susceptible mice.
- Assessed CM development and severity.
- Evaluated PbA antigen-specific interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) levels.
Main Results:
- Higher IL-10 mRNA levels were observed in the spleen and brain of resistant mice.
- Neutralization of IL-10 in resistant mice led to CM development in 35.7% of cases.
- Recombinant IL-10 administration protected susceptible mice against CM.
- IL-10 inhibited PbA antigen-specific IFN-gamma production in vitro but did not affect serum TNF levels in vivo.
Conclusions:
- Interleukin-10 (IL-10) plays a significant protective role in experimental cerebral malaria.
- Modulating IL-10 levels could be a therapeutic strategy for CM.
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