Inhibition of contact hypersensitivity with different analogs of benzoporphyrin derivative.
Four structural analogs of benzoporphyrin derivative (BPD), a potent anti-tumor photosensitizer, were evaluated for their capacity to influence the immunologically-mediated contact hypersensitivity (CHS) response against the hapten 2,4-dinitrofluorobenzene (DNFB). Immunocompetent hairless strain mice received BPD monoacid ring A (BPD-MA, verteporfin) and returned to normal housing conditions or treated with 690 nm red light (transcutaneous photodynamic therapy, PDT). Unexpectedly, we found that mice given BPD-MA exhibited significantly reduced CHS ear swelling responses to DNFB upon antigenic challenge, whether or not they had been treated with PDT. A significant reduction in the CHS response to DNFB was observed when BPD-MA or PDT was given 48 or 24 h prior to, on the same day, or 24 or 72 h after DNFB sensitization. However, the magnitude of the CHS response was unaffected if these treatments were given 96 h after DNFB sensitization, 24 h before challenge with DNFB. Significantly reduced CHS responses also occurred in Balb/c mice given BPD-MA with or without PDT. Mice given BPD-MA but retained in total darkness throughout the experimental period generated full-fledged ear swelling responses to DNFB indicating that CHS suppression with BPD-MA was light dependent. BPD monoacid ring B (BPD-MB) strongly reduced the CHS response of Balb/c mice kept under ambient light while BPD diacid ring A (BPD-DA) and BPD diacid ring B (BPD-DB) also lowered the CHS response but were less effective than the monoacid forms. Other photosensitizers including Photofrin, tin etiopurpurin, and zinc phthalocyanine did not alter the CHS response of Balb/c mice maintained under ambient light. The ability of different BPD analogs to inhibit the CHS response in mice held under ambient light conditions appears related to the potent photosensitizing activity of these compounds.
Simkin
G O
GO
QLT PhotoTherapeutics Inc., Vancouver, BC, Canada.
King
D E
DE
Levy
J G
JG
Chan
A H
AH
Hunt
D W
DW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D003877:Dermatitis, Contact / Q000188:drug therapy*; D004139:Dinitrofluorobenzene; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D000077362:Verteporfin
D000276:Adjuvants, Immunologic; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C504224:benzoporphyrin D; D004139:Dinitrofluorobenzene