N-acetyl-L-cysteine inhibits bleomycin-induced interleukin-8 secretion by bronchial epithelial cells.

Abstract

OBJECTIVE:

Bleomycin (BLM) has proven effective for the treatment of cancers, but the most serious dose-limiting side-effect is the development of pulmonary toxicity. Although the precise mechanism in the pathogenesis of BLM-induced lung injury has not been determined, oxygen radicals and neutrophils are indicated to play a key role in it. Interleukin-8 (IL-8) is thought to be an important mediator of the pathogenesis of acute lung injury.

METHODOLOGY:

The IL-8 production from bronchial epithelial cell line, BEAS-2B cells was measured by enzyme-linked immunosorbent assays for IL-8.

RESULTS:

The concentrations of IL-8 were reportedly elevated in BLM-induced lung injury, suggesting the involvement of IL-8 in the pathogenesis of BLM-induced lung injury. In the present study, we showed that BLM induced the expression of IL-8 protein and mRNA in BEAS-2B cells, and N-acetyl-L-cysteine (NAC) inhibited IL-8 expression. In addition, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC) also effectively inhibited BLM-induced IL-8 production.

CONCLUSION:

These results suggest that anti-oxidant-sensitive mechanism might be involved in the inhibition of IL-8 secretion by BLM-stimulated bronchial epithelial cells and that NAC might be useful for the treatment of BLM-induced lung injury.

• Authors: Y Gon, S Hashimoto, T Nakayama, K Matsumoto, T Koura, I Takeshita, T Horie
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 5 Issue 4 Pg. 309-13 (Dec 2000) ISSN: 1323-7799 [Print] Australia
• PMID: 11192539 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Antioxidants
• Free Radical Scavengers
• Interleukin-8
• Pyrrolidines
• Thiocarbamates
• Bleomycin
• pyrrolidine dithiocarbamic acid
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Antimetabolites, Antineoplastic (adverse effects)
• Antioxidants (pharmacology)
• Bleomycin (adverse effects)
• Bronchi (cytology, drug effects)
• Cell Line
• Drug Evaluation, Preclinical
• Enzyme-Linked Immunosorbent Assay
• Free Radical Scavengers (pharmacology)
• Humans
• Interleukin-8 (analysis, immunology, metabolism)
• Pyrrolidines (pharmacology)
• Respiratory Distress Syndrome (chemically induced, immunology, prevention & control)
• Respiratory Mucosa (drug effects, metabolism)
• Thiocarbamates (pharmacology)