Metabolic and cytokine responses to a second immunological
challenge with lps in mice with t. gondii infection.
Arsenijevic, D., L. Girardier, J. Seydoux, J. C. Pechere, I. Garcia,
R. Lucas, H. R. Chang, and A. G. Dulloo.
Departments of Physiology, Microbiology, Pathology and Internal
Medicine, Faculty of Medicine, University of Geneva, 1211 Geneva 4,
Switzerland, and Laboratory of Nutrition/Infection 5, Beth Israel
Deaconess Medical Center, West Campus, Harvard Medical School,
Boston, MA02215, USA.
APStracts 4:0262E, 1997.
Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss
Webster mice results in (i) an acute phase of infection lasting for
2-3 wks, characterized by weight loss, and (ii) a chronic phase in
which surviving mice show either partial weight recovery (Gainers) or
persistent though stable cachexia (Non-Gainers). In response to a
second immunological stimulation with LPS in the chronic phase of the
infection, it is shown that (a) the increase in energy expenditure
was more prolonged in both groups of infected mice than in controls,
(b) the intensity and duration of hypophagia were also differently
affected with Non-Gainers > Gainers > controls, and (c) the
infected mice had higher serum levels of TNF-, IL-10, and lower ratio
of IL-10:TNF- than controls; in contrast serum IL-4 increased to the
same level in all three groups. Evaluation of the permeability of the
blood-brain-barrier by i.v. injection of Evans blue revealed a marked
staining only in the brain of the infected Non-Gainers. Taken
together, these results indicate that in mice with chronic
Toxoplasmosis, a second non-specific challenge (with LPS) exacerbates
the hypophagic and hypermetabolic states, the latter being associated
with hyper-responsiveness in TNF- and IL-10 production. Furthermore,
the greater exacerbation of the hypophagic state in mice showing
persistent cachexia may be due to a pre-existing higher permeability
of the blood-brain-barrier which would allow a greater access of
plasma-borne cytokines and/or other neuroimmunologically active
substances to the central nervous system.
Received 6 May 1997; accepted in final form 12 November 1997.
APS Manuscript Number E209-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997