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Infection and Immunity, September 1999, p. 4435-4442, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice

Ching Li,1 Inés Corraliza,2 and Jean Langhorne1,3,*

Imperial College of Science, Technology and Medicine, London SW7 2AZ,1 and National Institute for Medical Research, London NW7 1AA, United Kingdom2, and 3Department of Biochemistry and Molecular Biology, Faculty of Veterinary Science, Universidad de Extremadura, 10071 Cáceres, Spain

Received 22 March 1999/Returned for modification 26 April 1999/Accepted 21 June 1999

Infection of interleukin-10 (IL-10)-nonexpressing (IL-10-/-) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10-/- mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10-/- mice produced more gamma interferon (IFN-gamma ), tumor necrosis factor alpha (TNF-alpha ), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-gamma in IL-10-/- mice by the injection of anti-IFN-gamma antibodies or by the generation of IL-10-/- IFN-gamma receptor-/- double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-gamma -independent pathways may be responsible for these pathological features of P. chabaudi malaria and may be due to direct stimulation of TNF-alpha by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-gamma or TNF-alpha produced.

* Corresponding author. Mailing address: Division of Parasitology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom. Phone: 44-181-913 8628. Fax: 44-181-913 8605. E-mail: jlangho{at}nimr.mrc.ac.uk.

Infection and Immunity, September 1999, p. 4435-4442, Vol. 67, No. 9
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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