Abstract: Zymosan (Zy) has been shown to act as a pathogen-associated molecular pattern that activates the innate immune Toll-like receptor subtypes 2 and 6 (TLR2, TLR6). Systemic challenge with TLR2/6-agonists has been shown to mediate brain-controlled signs of sickness behavior amongst them fever, depressed motor activity, anorexia and adipsia. This study was designed to determine whether Zy as a further TLR2/6-agonist is also capable to induce similar sickness behavior responses during systemic Zy-induced inflammation as those observed with Mycoplasma-specific TLR2/6 agonists. In telemetrically monitored rats intraperitoneal treatment with 10 mg kg 1 Zy induced a moderate febrile response with significantly elevated abdominal temperatures ( T of about 1.2°C) for a period of about 4 h on the day of injection (day 1). Already at the end of day 1 temperature data of the Zy group returned to normal values of control animals and thereafter showed an almost identical circadian rhythm for the next 3 nights and 2 days. Zy-treated animals showed generally lower cumulative motor activities, however, significantly reduced only during night 1 and night 3. Cumulative food intake was significantly reduced during night 1 and night 2 in the Zy group, while no significant changes were measured for cumulative water intake. In line with the depressed food intake, Zy-treated rats developed a reduction in body weight gain that became significant on day 3 and day 4 after the injection. In conclusion, Zy-induced fever, anorexia and depressed motor activity seem to result from activation of cellular pathways involved in the TLR2/6-dependent innate immune responses.
Thomas Hubschle , Sandra Rafalzik , Rudiger Gerstberger and Joachim Roth , 2007. Induction of Fever and Sickness Behavior in Telemetrically Monitored Rats During Systemic Inflammation Induced by Zymosan . Journal of Animal and Veterinary Advances, 6: 569-575.