Altered energy balance and cytokine gene expression in a murine model of chronic infection with toxoplasma gondii. Arsenijevic, D., L. Girardier, J. Seydoux, H. R. Chang, and A. G. Dulloo. Department of Physiology, Faculty of Medicine, Centre Medical Universitaire, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland, and Laboratory of Nutrition/Infection, Deaconess Hospital, Harvard Medical School, Boston, MA02215, USA.
APStracts 4:0011E, 1997.
The energetics and cytokine profile of a mouse model of infection with Toxoplasma gondii were studied during both the acute and chronic phases of the infection. Comparison were made with ad libitum fed controls as well as weight-matched controls (i.e. controls underfed to achieve the same weight changes as the infected groups). The results indicate three distinct temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain. First, during day 1-7 after infection, although food intake was unaltered, the daily energy expenditure was significantly elevated (+ 30%, P<0.001), and this was associated with increased expression of TNF-[alpha], IL-1 and IL-5 (from day 1 onwards) and IFN-[tau] (from day 3 onwards). Second, the hypermetabolic state (and elevated TNF -[alpha], IL-1, IL-5 and IFN-[tau] mRNA expression) persisted during the subsequent development of anorexia and marked cachexia, with an elevation of mRNA expression of IL-2 coinciding with the onset of anorexia. At the end of the acute phase of cachexia, the dual anorectic and hypermetabolic states were associated with an elevation in mRNA expression of all cytokines examined, namely TNF-[alpha], IL -1[beta], IL-2, IL-4, IL-5, IL-6, IL10, and IFN-[tau]. Third, in the chronic phase of the infection, the mice could be divided into two sub-groups on the basis of whether they showed a partial weight recovery (the infected Gainers) or no weight regain (the infected Non-Gainers). The infected Gainers, while still hypophagic relative to non-infected controls, were no longer hypermetabolic and their cytokine mRNA were no longer elevated, except for TNF-[alpha] and IL -10. In contrast, the infected Non-Gainers continued to show both anorexia and hypermetabolism, which were associated with an elevation in mRNA expression of all cytokines examined, and those of the TH2 profile (IL-4, IL-5) as well as IL-6 were more elevated than during acute cachexia. Taken together, these studies characterize the temporal changes in energy balance regulation following Toxoplasma gondii infection, and reveal distinct pattern of cytokine mRNA expression underlying (i) hypermetabolism versus anorexia (ii) acute versus chronic cachexia, and (iii) stable weight loss versus partial weight recovery. 

Received 15 October 1996; accepted in final form 31 December
1996.
APS Manuscript Number E512-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997