Anti-endotoxin hyperimmune globulin attenuates portal cytokinaemia, phagocytic cell priming, and acute lung injury after lower limb ischaemia-reperfusion injury.

Abstract

OBJECTIVES:

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.

DESIGN:

Prospective, randomised placebo controlled trial, animal experiment.

MATERIALS AND 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.

• Authors: D W Harkin, R Arnold, M Hoper
• Journal: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (Eur J Vasc Endovasc Surg) Vol. 33 Issue 3 Pg. 330-9 (Mar 2007) ISSN: 1078-5884 [Print] England
• PMID: 17161961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Endotoxins
• Immunoglobulin G
• Immunoglobulins
• Tumor Necrosis Factor-alpha
• antilipopolysaccharide antibodies
• Oxygen

Topics

• Animals
• Bacterial Translocation (immunology)
• Cytokines
• Disease Models, Animal
• Endotoxins (chemistry)
• Hindlimb (blood supply)
• Immunoglobulin G (pharmacology)
• Immunoglobulins (pharmacology)
• Luminescent Measurements
• Male
• Manometry
• Oxygen (blood)
• Partial Pressure
• Phagocytosis (drug effects, immunology)
• Portal System (immunology)
• Portal Vein (chemistry)
• Prospective Studies
• Random Allocation
• Reperfusion Injury (immunology)
• Respiratory Burst (immunology)
• Respiratory Distress Syndrome (immunology)
• Swine
• Tumor Necrosis Factor-alpha (blood)