Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation

作者: D. Rocksén , B. Lilliehöök , R. Larsson , T. Johansson , A. Bucht

DOI: 10.1046/J.1365-2249.2000.01373.X

关键词:

摘要: Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, anti-inflammatory effects anti-oxidant N-acetylcysteine (NAC) and glucocorticoid dexamethasone were investigated mice exposed to aerosolized (lipopolysaccharide (LPS)). Powerful reduction neutrophils bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection (10 mg/kg), whereas treatment with NAC only resulted when administered at high dose (500 mg/kg). Measurement cytokine chemokine expression lung tissue revealed significant decrease tumour necrosis factor-alpha, IL-1alpha, IL-1beta IL-6, IL- 12p40, MIP-1alpha mRNA where treated but not NAC. Analysis oxidative burst demonstrated remarkable oxygen radicals BALF after dexamethasone, effect significantly different from that untreated animals. conclusion, exerted both anti-oxidative airway inflammation, probably blocking early events inflammatory cascade. contrast, weak response no inhibition proinflammatory cytokines or neutrophils. These results demonstrate dramatic differences efficiency also indicate two drugs have actions. Combined additive action synergy observed.

参考文章(29)
I Ziment, Acetylcysteine: a drug that is much more than a mucokinetic. Biomedicine & Pharmacotherapy. ,vol. 42, pp. 513- 519 ,(1988)
Peter Moldéus, Ian A. Cotgreave, [48] N-acetylcysteine Methods in Enzymology. ,vol. 234, pp. 482- 492 ,(1994) , 10.1016/0076-6879(94)34119-2
Stephen D. Wolpe, Anthony Cerami, Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. The FASEB Journal. ,vol. 3, pp. 2565- 2573 ,(1989) , 10.1096/FASEBJ.3.14.2687068
N. Auphan, J. A. DiDonato, C. Rosette, A. Helmberg, M. Karin, Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis Science. ,vol. 270, pp. 286- 290 ,(1995) , 10.1126/SCIENCE.270.5234.286
Thomas Asquith, Steven L. Kunkel, Kevin E. Driscoll, Carl Johnston, Robert J. Isfort, Janet M. Carter, Brian W. Howard, Phillippe Detilleux, Alpha-quartz-induced chemokine expression by rat lung epithelial cells: effects of in vivo and in vitro particle exposure. American Journal of Pathology. ,vol. 149, pp. 1627- 1637 ,(1996)
T S Blackwell, B W Christman, J W Christman, E P Holden, T R Blackwell, In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. Journal of Immunology. ,vol. 157, pp. 1630- 1637 ,(1996)
Steven L. Kunkel, Nicholas Lukacs, Jeffrey H. Ruth, Stephen W. Chensue, Kelly Warmington, Mycobacterial and schistosomal antigen-elicited granuloma formation in IFN-gamma and IL-4 knockout mice: analysis of local and regional cytokine and chemokine networks. Journal of Immunology. ,vol. 159, pp. 3565- 3573 ,(1997)
J S Brower, E S Fox, J M Bellezzo, K A Leingang, N-acetylcysteine and alpha-tocopherol reverse the inflammatory response in activated rat Kupffer cells. Journal of Immunology. ,vol. 158, pp. 5418- 5423 ,(1997)
R. I. Scheinman, P. C. Cogswell, A. K. Lofquist, A. S. Baldwin, Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids Science. ,vol. 270, pp. 283- 286 ,(1995) , 10.1126/SCIENCE.270.5234.283