Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii

Abstract

The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

Decreased infarct size after focal cerebral ischemia in mice chronically infected with Toxoplasma gondii

“…Mice were chronically infected by i.p. injection of 10 cysts of Toxoplasma gondii (Me49 strain obtained from Dr A. Hemphill, University of Bern, Switzerland) (Arsenijevic et al, 1997). Less than 5% of mice died due to infection during weeks 2 and 3.…”

“…After this time point all infected mice survived. Acute infection with Toxoplasma gondii results in anorexia and body weight loss (Arsenijevic et al, 1997). We followed infected mice body weight and food intake 7 days before infection and up to 28 days (chronic phase) after infection (nϭ10).…”

“…We followed infected mice body weight and food intake 7 days before infection and up to 28 days (chronic phase) after infection (nϭ10). In the chronic phase of infection, some of these mice may show a partial weight regain (50%) or no weight regain (50%) (Arsenijevic et al, 1997). For all experiments, we used only the latter type of mice since these animals had higher basal brain cytokine levels and were expected to maximally respond to a new inflammation (Arsenijevic et al, 1998).…”

“…At the end of the perfusion the whole brains were quickly dissected out and frozen. Total RNA was prepared as described before (Arsenijevic et al, 1997). Northern blot analyses were performed using the mouse UCP2 or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) cDNA labeled with 32 P under standard conditions.…”

“…Chronic murine toxoplasmosis may be of particular interest in the study of infection-related effects on brain ischemia since it is associated with a tissue-specific regulation of the oxidative state (Arsenijevic et al, 2001) as well as activation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF␣), interferon-gamma (IFN␥) and interleukin-2 (IL-2), but also anti-inflammatory cytokines such as interleukin-10 (IL-10) (Arsenijevic et al, 1997(Arsenijevic et al, , 1998. Some of these cytokines are known to enhance neurodegeneration following ischemia (Arsenijevic et al, 2006).…”