title: Complement component c5a is integral to the febrile response of mice to lipopolysaccharide.
abstract: OBJECTIVE
  The complement system is critical to the febrile response of mice to intraperitoneally administered lipopolysaccharide (LPS). We previously identified C3 and C5 as two components potentially involved in this response. This study was designed to examine whether the complement system is also pivotal in the response of mice to intravenously or intracerebroventricularly injected LPS, to distinguish between C3 and C5 and their cognate derivatives as the essential mediator(s), and to determine whether the failure of complement-deficient mice to develop a fever could be due to their possible inability to secrete pyrogenic cytokines.
  
  
  METHODS
  Wild-type (WT; C57BL/6J) mice, hypocomplemented or not by intravenously injected cobra venom factor (10 U/mouse), and C3-, CR3- and C5-sufficient and -deficient mice were intravenously challenged with LPS (0.25 mug/mouse); WT and C3-/- mice pretreated with a C5a receptor antagonist (C5aRa) were similarly challenged. In addition, the serum levels of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6 were compared in LPS-treated C5+/+ and C5-/- mice.
  
  
  RESULTS
  LPS induced a 1 degrees C rise in core temperature in all the mice, except C5-/- mice and those pretreated with C5aRa. C5+/+ and C5-/- mice challenged intracerebroventricularly with LPS exhibited identical febrile responses. LPS induced similar increases in the serum levels of IL-1beta, TNFalpha and IL-6 in C5+/+ and C5-/- mice.
  
  
  CONCLUSIONS
  C5a is crucial for the development of febrile responses to LPS in mice; its site of action is peripheral, not central. The possibility that an inability to produce cytokines could account for the failure of C5-/- mice to develop a fever is not supported.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. lshuxin@physio1.utmem.edu
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: S A
authors.initials: SA
authors.lastname: Boackle
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
authors.forename: J D
authors.initials: JD
authors.lastname: Lambris
authors.forename: C M
authors.initials: CM
authors.lastname: Blatteis
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics / Q000276:immunology; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D003176:Complement C3; D016207:Cytokines; D004546:Elapid Venoms; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D044087:Receptor, Anaphylatoxin C5a; C016310:cobra venom factor; D015936:Complement C5a