COMPARATIVE-STUDIES ON THE TOLERANCE TO PHOTOINDUCED CUTANEOUS INFLAMMATORY REACTIONS BY PSORALEN AND ROSE-BENGAL

The photochemotherapeutic value of topical 8-methoxypsoralen (8-MOP) p lus UVA irradiation has been well recognized. The phototoxicity associ ated with psoralen plus UVA (PUVA) therapy is hallmarked by an increas e in vascular permeability (iVP), the accumulation of polymorphonuclea r leukocytes (aPMN) and erythema formation in situ. Rose bengal (RB) p lus UVA-VIS light (320-700 nm) produces a similar acute inflammatory r esponse, but without immediate or delayed erythema and perceptible ede ma, This study describes some of the parameters involved in inflammato ry reactions evoked by PUVA and the results are compared with RB-induc ed phototoxic reactions, The rates of iVP and aPMN with a 3 h pulse we re quantified using I-125-albumin and Cr-51-labelled PMNs respectively . The erythemal response was graded visually. 8-MOP cream was applied topically, while RB was injected intradermally in rabbit skin before U VA-VIS (9.4 J cm(-2)) irradiation. The data show that there is no sign ificant difference in the rates of iVP, aPMN and erythema formation be tween normal skin sites and mast cell-depleted skin sites when challen ged with 8-MOP plus light. These results suggest that in situ mast cel ls do not play a significant role in 8-MOP-photoinduced acute cutaneou s 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 d ays, 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 challenge d with RB plus light. Similarly, RB-photo-desensitized sites do not pr oduce iVP and aPMN of the same magnitude as the native skin sites when challenged with 8-MOP plus light. The desensitization and cross-desen sitization of skin sites to 8-MOP- or RB-photoinduced reactions sugges t that there is either direct attack on the target cell(s), thereby re moving the ability to express adhesion molecules, such as endothelial leukocyte adhesion molecule 1 (ELAM-1) or intercellular adhesion molec ule 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-I) and tumor necrosis factor alpha (TNF-alpha), res ponsible for the initiation and progression of cutaneous inflammations . (C) 1997 Elsevier Science S.A.