title: Comparative studies on the tolerance to photoinduced cutaneous inflammatory reactions by psoralen and rose bengal.
abstract: The photochemotherapeutic value of topical 8-methoxypsoralen (8-MOP) plus UVA irradiation has been well recognized. The phototoxicity associated with psoralen plus UVA (PUVA) therapy is hallmarked by an increase in vascular permeability (iVP), the accumulation of polymorphonuclear leukocytes (aPMN) and erythema formation in situ. Rose bengal (RB) plus UVA-VIS light (320-700 nm) produces a similar acute inflammatory response, but without immediate or delayed erythema and perceptible edema. This study describes some of the parameters involved in inflammatory reactions evoked by PUVA and the results are compared with RB-induced phototoxic reactions. The rates of iVP and aPMN with a 3 h pulse were quantified using 125I-albumin and 51Cr-labelled PMNs respectively. The erythemal response was graded visually. 8-MOP cream was applied topically, while RB was injected intradermally in rabbit skin before UVA-VIS (9.4 J cm-2) irradiation. The data show that there is no significant difference in the rates of iVP, aPMN and erythema formation between normal skin sites and mast cell-depleted skin sites when challenged with 8-MOP plus light. These results suggest that in situ mast cells do not play a significant role in 8-MOP-photoinduced acute cutaneous inflammatory reactions, in contrast with RB-photoinduced reactions. The iVP and aPMN responses are minimal or absent in sites subjected to repeated exposure to 8-MOP plus light for three or more consecutive days, suggesting the establishment of a desensitized/unresponsive state. Moreover, 8-MOP-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the normal (naive) skin sites when challenged with RB plus light. Similarly, RB-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the native skin sites when challenged with 8-MOP plus light. The desensitization and cross-desensitization of skin sites to 8-MOP- or RB-photoinduced reactions suggest that there is either direct attack on the target cell(s), thereby removing the ability to express adhesion molecules, such as endothelial leukocyte adhesion molecule 1 (ELAM-1) or intercellular adhesion molecule 1 (ICAM-1), involved in the accumulation of inflammatory cells, or downregulation of the secretion/release of putative agent(s), such as interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), responsible for the initiation and progression of cutaneous inflammations.
authors.affiliation: Department of Medicine, University of Toronto, Ont., Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Kumar
authors.forename: H F
authors.initials: HF
authors.lastname: Haberman
authors.forename: N S
authors.initials: NS
authors.lastname: Ranadive
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000276:immunology*; D003888:Desensitization, Immunologic; D004890:Erythema / Q000209:etiology; D005363:Ficusin / Q000633:toxicity*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008730:Methoxsalen / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D011701:PUVA Therapy / Q000009:adverse effects; D011817:Rabbits; D012395:Rose Bengal / Q000633:toxicity*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D012395:Rose Bengal; D003189:p-Methoxy-N-methylphenethylamine; D005363:Ficusin; D008730:Methoxsalen