Protective effect of N-acetylcysteine in hapten-induced irritant and contact hypersensitivity reactions.
The hapten-induced irritant and contact hypersensitivity reactions are experimental models of cutaneous inflammation in which tumor necrosis factor-alpha is an important mediator. N-acetylcysteine is an anti-oxidant that inhibits the action of the nuclear factor-kB, which promotes the transcription of many genes, including the gene for tumor necrosis factor-alpha. We tested the ability of N-acetylcysteine to antagonize the development of the irritant and contact hypersensitivity reactions induced by the epicutaneous application of trinitrochlorobenzene in mice. Systemic and topical treatment with N-acetylcysteine reduced skin swelling in both the irritant and contact hypersensitivity reactions; in the latter it also reduced the dermal leukocyte infiltrate. It also reduced the cutaneous expression of the mRNA for tumor necrosis factor-alpha in both conditions. These results show that N-acetylcysteine antagonizes the development of irritant and contact hypersensitivity reactions and that its action includes a reduction in the expression of tumor necrosis factor-alpha mRNA. N-acetylcysteine may be useful in the treatment of cutaneous inflammation mediated by tumor necrosis factor-alpha.
Senaldi
G
G
Department of Pathology, University of Geneva, Switzerland.
Pointaire
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P
Piguet
P F
PF
Grau
G E
GE
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006241:Haptens / Q000009:adverse effects*; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010853:Picryl Chloride / Q000009:adverse effects; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics
D006241:Haptens; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine; D010853:Picryl Chloride