Anti-endotoxin hyperimmune globulin attenuates portal cytokinaemia, phagocytic cell priming, and acute lung injury after lower limb ischaemia-reperfusion injury.
OBJECTIVE
Acute limb ischaemia is a common and often lethal clinical event. Reperfusion of an ischaemic limb has been shown to induce a remote gut injury associated with transmigration of endotoxin into the portal and systemic circulation, which in turn has been implicated in the conversion of the sterile inflammatory response to a sepsis syndrome, after lower torso ischaemia-reperfusion injury. This study tests the hypothesis that an anti-endotoxin hyperimmune globulin attenuates ischaemia-reperfusion (I/R) associated sepsis syndrome.


METHODS
Prospective, randomised placebo controlled trial, animal experiment.


METHODS
Experimental porcine model, bilateral hind limb I/R injury, randomised to receive anti-endotoxin hyperimmune globulin or placebo.


RESULTS
Bilateral hind limb I/R injury significantly increased intestinal mucosal acidosis, portal endotoxaemia, plasma cytokine (TNF-alpha, IL-6, IL-8) concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, oedema, and capillary-alveolar protein leak. Conversely, pigs treated with anti-endotoxin hyperimmune globulin (IgG) 20mg/kg at onset of reperfusion had significantly reduced portal endotoxaemia, early circulating phagocytic cell priming, plasma cytokinaemia and attenuation of acute lung injury.


CONCLUSIONS
Endotoxin translocation across a hyperpermeable gut barrier, phagocytic cell priming and cytokinaemia are key events of limb I/R injury induced systemic inflammation and acute lung injury. This study shows that an anti-endotoxin hyperimmune globulin attenuates portal endotoxaemia, which may reduce early phagocytic cell activation, cytokinaemia and ultimately acute lung injury.
Harkin
D W
DW
Regional Vascular Surgical Unit, The Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK. d.w.harkin@qub.ac.uk
Arnold
R
R
Hoper
M
M
D000818:Animals; D018988:Bacterial Translocation / Q000276:immunology; D016207:Cytokines; D004195:Disease Models, Animal; D004731:Endotoxins / Q000737:chemistry; D006614:Hindlimb / Q000098:blood supply*; D007074:Immunoglobulin G / Q000494:pharmacology*; D007136:Immunoglobulins / Q000494:pharmacology*; D008163:Luminescent Measurements; D008297:Male; D008365:Manometry; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D011168:Portal System / Q000276:immunology*; D011169:Portal Vein / Q000737:chemistry; D011446:Prospective Studies; D011897:Random Allocation; D015427:Reperfusion Injury / Q000276:immunology*; D016897:Respiratory Burst / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D004731:Endotoxins; D007074:Immunoglobulin G; D007136:Immunoglobulins; D014409:Tumor Necrosis Factor-alpha; C042866:antilipopolysaccharide antibodies; D010100:Oxygen