title: Characterizing the immunological effects of oral healthcare ingredients using an in vitro reconstructed human epithelial model.
abstract: Oral healthcare products are well tolerated and while adverse occurrences are rare there is still a need to explore the interaction between these products and the oral mucosa. This study assessed the effects of oral healthcare ingredients: sodium lauryl sulphate (SLS), a detergent; cinnamic aldehyde (CA), a flavouring agent; and cetylpyridinium chloride (CPC), an antiseptic, using a reconstructed human oral mucosal model (OMM). Differential release of inflammatory cytokines IL-1α, IL-8 and cytotoxicity was compared with other known irritants and sensitizers to identify a signature response profile that could be associated with oral mucosal irritation. Response profiles differed with irritants being more cytotoxic. CA and control sensitizers nickel sulphate (NiSO4) and 1-chloro-2,4-dinitrochlorobenzene (DNCB) released lower levels of IL-1α than CPC and control irritant benzalkonium chloride (BC), whereas the opposite was observed for IL-8. Significant levels of IL-8 and IL-1α were released with 5-15 mg/ml (0.5-1.5% w/v) SLS. Quantitative PCR indicated that cytokine release at lower SLS concentrations is not entirely due to cell necrosis but in part due to de novo synthesis. These findings suggest that the OMM can be used to predict oral irritation thus making it a potentially valuable model for screening new oral healthcare ingredients prior to clinical release.
authors.affiliation: Bart's and the London School of Medicine and Dentistry, Queen Mary University, UK. Electronic address: e.hagi-pavli@qmul.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Hagi-Pavli
authors.affiliation: Bart's and the London School of Medicine and Dentistry, Queen Mary University, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Williams
authors.affiliation: GSK Oral Healthcare R & D, Weybridge, Surrey, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Rowland
authors.affiliation: School of Clinical Dentistry, University of Sheffield, UK.
authors.forename: M
authors.initials: M
authors.lastname: Thornhill
authors.affiliation: Bart's and the London School of Medicine and Dentistry, Queen Mary University, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Cruchley
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D002594:Cetylpyridinium / Q000494:pharmacology*; D003802:Dentifrices / Q000009:adverse effects / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005421:Flavoring Agents / Q000494:pharmacology*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009061:Mouth Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*
chemical_list: D000891:Anti-Infective Agents, Local; D003802:Dentifrices; D003902:Detergents; D005421:Flavoring Agents; D053582:Interleukin-1alpha; D016209:Interleukin-8; D012967:Sodium Dodecyl Sulfate; D000171:Acrolein; D002594:Cetylpyridinium; D007770:L-Lactate Dehydrogenase; C012843:cinnamaldehyde
keywords: Cinnamic aldehyde; Human oral mucosal model; Inflammatory cytokines; Irritant; Sensitizer; Sodium lauryl sulphate (SLS)