METABOLIC-CYTOKINE RESPONSES TO A 2ND IMMUNOLOGICAL CHALLENGE WITH LPS IN MICE WITH TOXOPLASMA-GONDII INFECTION

Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss We bster mice results in 1) an acute phase of infection lasting for 2-3 w k, characterized by weight loss, and 2) a chronic phase in which survi ving mice show either partial weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers). In response to a second immun ological stimulation with lipopolysaccharide (LPS) in the chronic phas e of the infection, it is shown that 1) the increase in energy expendi ture was more prolonged in both groups of infected mice than in contro ls, 2) the intensity and duration of hypophagia were also differently affected with Nongainers > Gainers > controls, and 3) the infected mic e had higher serum levels of tumor necrosis factor-alpha (TNF-alpha) a nd interleukin (IL)-10 and a lower ratio of IL-10 to TNF-alpha than co ntrols. In contrast, serum IL-4 increased to the same level in all thr ee groups. Evaluation of the permeability of the blood-brain barrier b y intravenous injection of Evans blue revealed a marked staining in th e brain of only the infected Nongainers. Taken together, these results indicate that, in mice with chronic toxoplasmosis, a second nonspecif ic challenge (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being associated with hyperresponsiveness in TNF-al pha and IL-10 production. Furthermore, the greater exacerbation of the hypophagic state in mice showing persistent cachexia may be due to a preexisting higher permeability of the blood-brain barrier, which woul d allow a greater access of plasma-borne cytokines and/or other neuroi mmunologically active substances to the central nervous system.