Afloqualone Photosensitivity. Immunogenicity of Afloqualone‐photomodified Epidermal Cells

Abstract

Afloqualone (AQ) is an oral muscle relaxant and evokes ultraviolet A (UVA)-induced photosensitivity dermatitis as a side effect. Histologic observations of the skin eruption suggest that AQ photosensitivity is mediated not only by phototoxic but also by photoallergic mechanisms. To address the immunological mechanisms of AQ photosensitivity, we examined the immunogenicity of AQ-photomodified epidermal cells in mice. Afloqualone was covalently coupled with bovine serum albumin by irradiation with UVA but not UVB. Because of this ability of AQ to photobind to protein, murine epidermal cells were easily modified with AQ by exposure to UVA. Subcutaneous inoculation of AQ-photomodified epidermal cells successfully induced an antigen-specific delayed-type hypersensitivity in mice. These findings suggest that AQ-photoderivatized epidermal cells are highly immunogenic and that photomodification of epidermal cells with AQ is an initial event to evoke AQ photosensitivity dermatitis.

Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA

“…The phototoxicity is mediated by reactive oxygens, in particular singlet oxygen [11], while the photoallergenicity occurs as a consequence of immunological events, where the UVinduced formation of photoantigen triggers T cell responses [8][9][10]. Recently, the incidence of the photoallergic type is higher than that of the phototoxic one [1,6,7]. Our studies have suggested that the vast majority of clinically photoallergic chemicals are photohaptens that bind covalently to protein under exposure to UV [1,6,7,9].…”

“…Recently, the incidence of the photoallergic type is higher than that of the phototoxic one [1,6,7]. Our studies have suggested that the vast majority of clinically photoallergic chemicals are photohaptens that bind covalently to protein under exposure to UV [1,6,7,9].…”

“…More recent causative agents are cosmetic or sunscreen products such as 6-methylcoumarin, musk ambtette, benzophenone, and non-steroidal anti-inflammatory drugs [4]. Likewise, there have been various culprit drugs to evoke photosensitivity, including chlorpromazine, quinolones, such as sparfloxacin (SPFX) and enoxacin (ENX), piroxicum, afloqualone, and others [1,6,7].…”

“…The former disease is induced by skin application of a contactant and following exposure to ultraviolet light (UV) [2][3][4][5], while the latter is evoked by oral administration of a photosensitizing drug and subsequent exposure of the skin to UV [6][7][8][9][10]. In both diseases, the action spectrum is UVA in most cases, and UVB can exceptionally evoke the photosensitivity dermatitis [1,5,6].…”

Stimulation of Langerhans cells with ketoprofen plus UVA in murine photocontact dermatitis to ketoprofen

“…In general, photoreactions by photosensitive chemicals are divided into the phototoxic and photoallergic types. While phototoxicity is mediated by active oxygen, especially singlet oxygen [8,9], photoallergy occurs as a consequence of a specific immune reaction mediated by antigenspecific, sensitized T cells [10][11][12][13][14]. KP has both phototoxic and photoallergic potentials, but many clinical observations have indicated that photosensitivity to KP is a photoallergic reaction [1][2][3][4][5][6][7].…”