Thermal Response to Zymosan: The Differential Role of Complement

• Published in: Neuroimmunomodulation 2002-01, Vol.10 (2), p.122-128
• Main Authors: Li, Shuxin, Llanos-Q, Jose, Blatteis, Clark M.
• Format: Article
• Language: English
• Subjects: Animals; Complement Inactivator Proteins - pharmacology; Complement System Proteins - immunology; Complement System Proteins - metabolism; Elapid Venoms - pharmacology; Fever - chemically induced; Fever - immunology; Fever - physiopathology; Guinea Pigs; Immunity, Innate - physiology; Injections, Intraperitoneal; Male; Original Paper; Sodium Chloride - pharmacology; Zymosan
• ISSN: 1021-7401; 1423-0216
• DOI: 10.1159/000065187

Objectives: This study was designed to determine whether the complement (C) system may be involved in the febrile response to zymosan (Zym), a glycan derived from yeast cell walls. Methods: Cobra venom factor (CVF) at 100 U/animal or its vehicle, pyrogen-free saline (PFS), was injected intravenously (i.v.) into guinea pigs to deplete serum C. Eighteen hours later, a low or high dose of Zym or its vehicle, PFS, was administered i.v. or intraperitoneally (i.p.) to these animals. The core temperature (T c ) was measured continuously by thermocouples. Serum C levels were determined by sheep erythrocyte hemolytic assay. Results: Zym at 1 mg/kg caused a 1°C T c rise that was not significantly affected by CVF pretreatment. However, CVF-induced hypocomplementation converted the T c fall (∼1.2°C) produced by 100 mg/kg of Zym i.p. into a 1°C T c rise. Similarly, CVF pretreatment did not affect the T c rise caused by 0.5 mg/kg of Zym i.v., but converted the T c fall induced by 25 mg/kg i.v. into a 1°C T c rise. A separate experiment showed that 25, but not 0.5 mg/kg of Zym i.v., decreased serum C by 34% in 15 min; C did not recover over the next 6 h. A second i.v. injection of 25 mg Zym/kg 210 min later, when the T c had recovered but the serum C had not, yielded a smaller and briefer T c fall. Conclusion: These results suggest that Zym is inherently pyrogenic, but this effect is manifested only when the dose of zymosan is too small to activate C or when C has been reduced by prior activation.