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A protective role for IL-6 during early infection with Toxoplasma gondii

Jebbari, H and Roberts, C W and Ferguson, D J P and Bluethmann, H and Alexander, J and Roberts, Craig (1998) A protective role for IL-6 during early infection with Toxoplasma gondii. Parasite Immunology, 20 (5). pp. 231-239. ISSN 0141-9838

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Abstract

IL-6 deficient mice were found to be signifcantly more susceptible to peroral infection with Toxoplasma gondii than their wild-type counterparts as measured by survival, brain cyst burdens and brain pathology at 28 days postinfection. The physical manifestations of disease, such as weight loss, were not observed in IL-6 deficient animals until at least seven days later than such changes occurred in wild-type mice. During this early stage of infection IL-6+/+ but not IL-6-/- mice mounted a peripheral blood neutrophilia. Furthermore, between 6-8 days post-infection there was a significant increase in plasma IFN-gamma levels in wild-type but not IL-6 deficient mice. Not until days 18-23 post-infection, concurrent with the majority of deaths in IL-6-/- mice, were plasma IFN-gamma levels substantially and significantly raised in IL-6-/- mice. At this time not only were these plasma IFN-gamma levels 20-fold higher than background but eight-fold greater than peak (6-8 clays post-infection) IFN-gamma levels in IL-6+/+ mice. IFN-gamma dependent parasite specific IgG2a levels were also significantly higher in IL-6-/- mice over this period and thereafter Overall the evidence suggests that in the absence of IL-6 mice are unable to initiate a rapid proinflammatory response against T. gondii, which allows increased parasite growth. Increased mortality in IL-6-/- mice may be directly due to this increased parasite burden and the excessive inflammatory response this induces three weeks post-infection.