Complement C5 and early oxygen kinetics during murine sepsis.
OBJECTIVE
Changes in oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) are common but poorly understood features of sepsis. The authors studied the role of complement C5 in the development of abnormal oxygen kinetics during sepsis in mice, arguing that as a pro-inflammatory event, complement activation might exacerbate disturbances in oxygen use during abdominal sepsis.


METHODS
An open-circuit indirect calorimeter was used to measure VO(2), VCO(2), and respiratory exchange ratio during a seven-day median lethal dose (LD(50)) murine cecal ligation and puncture (CLP) model.


RESULTS
CLP produced significant changes in oxygen kinetics within three hours of onset, although when the animals were stratified by seven-day survival, no difference in these abnormalities was seen between the survivors and the nonsurvivors. Genetic deficiency of C5 did not ameliorate the changes in oxygen utilization. Rather, the C5-deficient mice experienced more severe abnormalities in oxygen kinetics and greater mortality. Treating animals with anti-C5a antibodies at the time of injury had little effect on oxygen kinetics, indicating that C5b, rather than C5a, was predominantly acting to protect the mice during the first 24 hours of illness.


CONCLUSIONS
These findings indicate that the primary contribution of C5 to oxygen kinetics during sepsis is salutary through the host defense conveyed by generation of C5b, rather than detrimental by worsening oxygen utilization via pro-inflammatory mechanisms.
Valencia
Gabriel
G
Department of Emergency Medicine, University of Michigan, Room 7679 Kresge Research Building I, 200 Zina Pitcher Place, Ann Arbor, MI 48019, USA.
Sarma
J Vidya
JV
Younger
John G
JG
D000818:Animals; D002153:Calorimetry, Indirect; D003167:Complement Activation; D003182:Complement C5 / Q000502:physiology*; D004195:Disease Models, Animal; D004546:Elapid Venoms; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D010101:Oxygen Consumption / Q000502:physiology; D018805:Sepsis / Q000276:immunology / Q000503:physiopathology*
D003182:Complement C5; D004546:Elapid Venoms