Benzalkonium chloride breaks down conjunctival immunological tolerance in a murine model.
The impact of topical eye drops with benzalkonium chloride (BAK) as a preservative could involve more than the reported toxic effects on the ocular surface epithelium and ultimately affect the immune balance of the conjunctiva. We found that BAK not only impairs tolerance induction in a murine model, but leads to mild systemic immunization. Contrasting with antigen only-treated mice, there was no induction of interleukin 10-producing antigen-specific CD4(+) cells in BAK-treated animals. Moreover, the tolerogenic capacity of migrating dendritic cells (DCs) was reduced, apparently involving differential conditioning by soluble epithelial factors. Accordingly, epithelial cells exposed in vitro to BAK were less suppressive and failed to induce tolerogenic DCs in culture. As this effect of BAK was dependent on epithelial nuclear factor κB pathway activation, our findings may provide new therapeutic targets. Thus, tolerance breakdown by BAK should be considered an important factor in the management of glaucoma and immune-mediated ocular surface disorders.
Immunology Laboratory, Institute of Experimental Medicine, National Academy of Medicine, Buenos Aires, Argentina. jeremiasg@gmx.net
J G
JG
Galletti
M L
ML
Gabelloni
P E
PE
Morande
F
F
Sabbione
M E
ME
Vermeulen
A S
AS
Trevani
M N
MN
Giordano
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects* / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D001548:Benzalkonium Compounds; D016328:NF-kappa B