Premium
Ocular granulomatosis associated with brimonidine treatment. Does brimonidine have an effect on human macrophages and dendritic cells in vitro?
Author(s) -
BOUABANE I,
MAURAGE CA,
LABALETTE M,
ROULAND JF,
LABALETTE P
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.t063.x
Subject(s) - brimonidine , medicine , blepharitis , immunology , uveitis , antigen presenting cell , benzalkonium chloride , immune system , pathology , t cell , ophthalmology , intraocular pressure
Purpose Conjunctival and episcleral granulomas with uveitis have been reported as a side effect of antiglaucomatous topical use of brimonidine tartrate. We postulated that brimonidine is implicated in this inflammatory process and studied its effects on the antigen presenting cells (APCs) cytokines production. Methods Conjunctival and episcleral granulomatous lesions were immunohistochemically analyzed for CD3, CD4, CD8, CD1a, CD11c, CD68, and CD123. Macrophages and dendritic cells (DCs) were generated from peripheral blood monocytes of healthy donors and of patients who presented uveitis and granulomatous ocular infiltration induced by brimonidine topical treatment. APCs were respectively exposed to preserved and unpreserved brimonidine tartrate suspension(0.012%),0.005% benzalkonium chloride (BAK) and lipopolysaccharides (LPS). APCs Th1/Th2 cytokines production was measured in supernatants by multiplex flow cytometry. Results The granulomas consisted predominantly of CD4+ T‐cells and APCs, i.e. epithelioid macrophages CD 68+ and myeloid DCs CD11c+. Comparative exposure of APCs to unpreserved or preserved brimonidine tartrate formulations, or BAK alone, induced similar amounts of pro (IL‐6 or TNF‐α) and anti (IL‐10) inflammatory cytokines. Brimonidine tartrate and BAK reduced the LPS‐stimulated production of IL‐6, TNF‐α and IL‐10. Conclusion The histhopathological analysis of the conjunctiva and the episclera identified the main cellular actors involved in the granulomatous inflammatory process. By altering the APCs IL‐10 production, brimonidine tartrate will affect induction of tolerance by DCs and allow initiation of immune response leading to granulomas formation.