Apoptosis in ibuprofen-induced Stevens-Johnson syndrome.
Cytokines play a role in the immunopathological and molecular mechanisms of drug-induced hypersensitivity reactions (HSR). The objective of the current report was to analyze the reliability and correlation between the clinical symptoms observed in a patient that presented an ibuprofen-induced Stevens-Johnson Syndrome (SJS), her lymphocyte toxicity assay to the incriminated drug, and the cytokine secretion in the patient's sera. In her skin biopsy, the apoptotic keratinocytes is shown. Clinically, the patient presented a triad that characterizes "true" HSR (rash, fever, and liver involvement). The pro-inflammatory cytokines were significantly higher in sera from the patient than in sera from control patients (analyzed previously in the authors' laboratory). More specifically, the high level of tumor necrosis factor alpha (TNF-alpha) is as high as in patients found to have toxic epidermal necrolysis (TEN) and presenting "true" HSR, eg, rash, fever, and organ involvement. The same is the case with the apoptotic markers Fas, caspase activity, and M30. T-cell cytokines control the pathogenesis of SJS/TEN contributing to apoptotic processes in the liver and in the skin.
Neuman
Manuela
M
In Vitro Drug Safety and Biotechnology Laboratory, University of Toronto, Toronto, Ontario, Canada. Manuela.Neuman@utoronto.ca
Nicar
Michael
M
D000293:Adolescent; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D012867:Skin / Q000201:enzymology / Q000473:pathology; D013262:Stevens-Johnson Syndrome / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases; D007052:Ibuprofen