Complement activation, endothelin-1 and neuropeptide Y in relation to the cardiovascular response to endotoxin-induced systemic inflammation in healthy volunteers.

• BACKGROUND: Endotoxin is a major stimulus for triggering the host response in septicaemia. The pathophysiology of sepsis involves activation of the vascular endothelium and leukocytes, resulting in the release of various mediators, e.g. cytokines, nitric oxide (NO), endothelin (ET-1) and complement factors. We evaluated the blood levels of complement activation, ET-1 and neuropeptide Y (NPY) in parallel with the haemodynamic and oxygen transport response during human experimental endotoxemia. METHODS: Eleven healthy men had venous, arterial and pulmonary arterial catheters placed for continuous haemodynamic measuring. After 30 min rest endotoxin (E. Coli 4 ng kg(-1), Lot G1) was intravenously administered. Blood samples from pulmonary and arterial catheters were collected hourly over 4 h. RESULTS: Body temperature augmented significantly from baseline values (36.7 +/- 0.7 degrees C, mean +/- SEM) with a maximum after 3.5 h (39.1 +/- 0.3 degrees C, P < 0.001). Cardiac output increased by 100%, systemic vascular resistance decreased by 50%, the oxygen consumption and the tissue oxygen transport increased. Activation of the complement system was indicated by an increase in SC5b-9. Endothelin-1-like immunoreactivity (ET-1-LI) increased over time in arterial blood. NPY-like immunoreactivity (NPY-LI) did not change over time. CONCLUSION: A dose of endotoxin associated with reproducible systemic vasodilation and fever in healthy subjects causes complement activation and increased systemic levels of ET-1-LI, illustrating that the model is a useful tool for inducing moderate systemic inflammation where several mediator systems are activated.

Nyckelord

Adult

Body Temperature

drug effects

Complement Activation

physiology

Endothelin-1

blood

Endotoxemia

physiopathology

Endotoxins

Hemodynamics

physiology

Humans

Inflammation

chemically induced

physiopathology

Male

Neuropeptide Y

blood

Oxygen Consumption

drug effects

Pulmonary Alveoli

metabolism

physiology

Pulmonary Gas Exchange

drug effects

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