Optimization of the THP-1 activation assay to detect pharmaceuticals with potential to cause immune mediated drug reactions

Corti, D; Galbiati, Valentina; Gatti, Nicolò; Marinovich, Marina; Galli, Corrado L.; Corsini, Emanuela

doi:10.1016/j.tiv.2015.04.012

Cited by 18 publications

(21 citation statements)

References 37 publications

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“…Based on the notion that drug sensitizers and chemical sensitizers share the same mode of action, we recently investigated the possibility to use the THP-1 activation assay developed for skin and respiratory sensitizers, for the in vitro identification of pharmaceuticals, which may be associated with in vivo drug hypersensitivity reactions (Corti et al, 2015 ). It is well known that allergen drugs share with chemical allergens common mechanisms of cell activation and for reason we propose the THP-1 activation assay also for the hazard identification of immune-mediated hypersensitivity reactions induced by pharmaceuticals.…”

Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%

“…Drugs were selected on the basis of clear in vivo immune-adverse reactions reported in literature, post-marketing data or labeling information, and on the commercial availability as pure drugs. Clonidine, ofloxacine, procainamide, streptozotocin, sulfamethoxazole which have been associated with a relatively high incidence of immune-mediated hypersensitivity reactions (Weaver et al, 2005 ), methyl salicylate and probenecid, which have been reported to cause irritant or allergic contact dermatitis and anaphylactic reactions (Corti et al, 2015 ), have been tested. We developed a strategy based on IL-8 production, CD86 and/or CD54 expression in THP-1 cells useful for the in vitro identification of drug sensitizers (see Figure 2 ).…”

Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%

“…As shown in Table 1 , the combination of both IL-8 and CD86 expression allows the identification of all drugs tested. The use of IL-8 mRNA expression at 3 h or CD54 expression at 24 h may offer an alternative to the 48 h exposure and increase our confidence in the negativity of a drug (see Corti et al, 2015 ). The expression of IL-8 mRNA at 3 h is based on previous observation we made on chemical allergens failing to induce the release of IL-8: all chemicals sensitizers tested including pro-hapten induced IL-8 mRNA at 3 h (Galbiati et al, 2012 ).…”

Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%

“…CD86 expression was evaluated by flow cytometric analysis. Original data are present in Corti et al ( 2015 ). Legend: – no induction observed.…”

Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%

“…The withdrawal from the market of drug is also an important economic issue due to the extremely high costs associated with the development of a drug (Pieters, 2007 ). The development of alternative in vitro assays to detect the sensitization potential during the development phase of a drug would increase safety and possibly reduces the risk of market withdrawal (Corti et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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In vitro Models to Evaluate Drug-Induced Hypersensitivity: Potential Test Based on Activation of Dendritic Cells

et al. 2016

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Hypersensitivity drug reactions (HDRs) are the adverse effect of pharmaceuticals that clinically resemble allergy. HDRs account for approximately 1/6 of drug-induced adverse effects, and include immune-mediated (“allergic”) and non-immune-mediated (“pseudo allergic”) reactions. In recent years, the severe and unpredicted drug adverse events clearly indicate that the immune system can be a critical target of drugs. Enhanced prediction in preclinical safety evaluation is, therefore, crucial. Nowadays, there are no validated in vitro or in vivo methods to screen the sensitizing potential of drugs in the pre-clinical phase. The problem of non-predictability of immunologically-based hypersensitivity reactions is related to the lack of appropriate experimental models rather than to the lack of -understanding of the adverse phenomenon. We recently established experimental conditions and markers to correctly identify drug associated with in vivo hypersensitivity reactions using THP-1 cells and IL-8 production, CD86 and CD54 expression. The proposed in vitro method benefits from a rationalistic approach with the idea that allergenic drugs share with chemical allergens common mechanisms of cell activation. This assay can be easily incorporated into drug development for hazard identification of drugs, which may have the potential to cause in vivo hypersensitivity reactions. The purpose of this review is to assess the state of the art of in vitro models to assess the allergenic potential of drugs based on the activation of dendritic cells.

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Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%

Section: Potential In Vitro Pre-clinical Tests To mentioning

confidence: 99%