Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.
Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation.
Chiang
Chi-Huei
CH
Chest Department, Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University Taipei, Taiwan, ROC. chiang01@vghtpe.gov.tw
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002196:Capillaries / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008297:Male; D018375:Neutrophil Activation / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1