Oxidative stress, inflammation and neutrophil superoxide release in patients with Crohn's disease: distinction between active and non-active disease.
Increased oxidative stress has been previously demonstrated in patients with Crohn's disease (CD). However, to date, this parameter has not been assessed in a comparative study of patients in prolonged remission and those with the active disease. We report here our study of lipid peroxidation, antioxidant and inflammation status in serum derived from 16 active CD patients, 27 clinically stable patients, and 15 healthy controls. Results The extent of lipid peroxidation was higher in CD patients than in the healthy controls, while the levels of lipid peroxides (PD) and of thiobarbituric acid-reactive substances (TBARS) were significantly (P < 0.01) higher in serum obtained from patients with active CD (22 and 30%, respectively) than in that obtained from patients in remission. An analysis of the antioxidant status revealed that the beta-carotene levels in sera derived from all CD patients - patients with active or stable CD (49.4 +/- 15 and 95.6 +/- 25 mg% beta-carotene, respectively) - were higher than that in the controls (145 +/- 40 mg%). Serum activity of glutathione peroxidase (GSH-Px) was significantly (P < 0.001) higher (by 31%) in the patients with active CD than in the control group. There was no significant difference in GSH-Px activity between patients in remission and the controls. In terms of the inflammatory status, we found significantly (P < 0.01) higher levels of C-reactive proteins (CRP) and of tumor necrosis factor alpha (TNFalpha) in patients with active CD than in CD patients in remission. There was a significant correlation between those parameters and the extent of lipid oxidation. Neutrophils, which are a potential source of oxygen-free radicals, were activated by incubation with phorbol myristate acetate (PMA). Superoxide and lysozyme release were significantly reduced in neutrophils derived from patients with active CD (by 25 and 28%, respectively) in comparison to the control group. However, stimulated neutrophils from stable patients demonstrated only a minimally non-significant lower release of superoxide and lysozyme compared to the controls. Conclusion The results obtained in this study demonstrate an enhanced inflammatory and oxidative stress and a decreased antioxidant status in patients with active CD. As the patients improved and became clinically stable, the oxidative parameters decreased, approaching normal values. As neutrophil activation was also lower in patients with active disease, neutrophil activation may represent a possible defense mechanism of the body against tissue injury.
Maor
Irit
I
Department of Biochemistry, Bnai-Zion Medical Center, Haifa, Israel. iritmaor@yahoo.com
Rainis
Tova
T
Lanir
Amos
A
Lavy
Alexandra
A
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003424:Crohn Disease / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019207:beta Carotene / Q000097:blood
D000975:Antioxidants; D018836:Inflammation Mediators; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D019207:beta Carotene; D013481:Superoxides; D002097:C-Reactive Protein; D005979:Glutathione Peroxidase; D009113:Muramidase