Abstract: Topical cilomilast (mouse study)
PDE4 Inhibition Suppresses IL17-Associated Immunity in Dry Eye Disease.
I haven't updated the clinical trial roster in eons but I think this is what I once had listed as Alcon's AL-43546.
To determine the effect of phosphodiesterase type-4 (PDE4) inhibition on IL17- associated immunity in experimental dry eye disease (DED).
Murine DED was induced, after which a PDE4 inhibitor (cilomilast), dexamethasone, cyclosporine, or a relevant vehicle was administered topically. Real-time polymerase chain reaction, immunohistochemical staining, and flow cytometry were employed to evaluate the immuno-inflammatory parameters of DED with a focus on IL17-associated immunity. Corneal fluorescein staining (CFS) was performed to evaluate clinical disease progression.
DED induction increased proinflammatory cytokine expression, pathogenic immune cell infiltration, and CFS scores. Cilomilast significantly decreased the expression of TNF-α in the cornea (P ≤0.05) and IL-1α, IL-1β, and TNF-α in the conjunctiva (P ≤0.05) as compared to vehicle control. Cilomilast treatment markedly decreased the presence of CD11b+ antigen-presenting cells in the central and peripheral cornea (P ≤0.05), and led to decreased conjunctival expression of cytokines IL-6, IL-23, and IL-17 (P ≤ 0.05). Moreover, cilomilast decreased the expression of IL-17 and IL-23 in the draining lymph nodes (P ≤0.05). Topical cilomilast was significantly more effective than vehicle at reducing CFS scores (P ≤ 0.05). The therapeutic efficacy of cilomilast was comparable or superior to that of dexamethasone and cyclosporine in all tested measures.
Topical cilomilast suppresses the generation of IL17-associated immunity in experimental DED.
Invest Ophthalmol Vis Sci. 2012 May 10. [Epub ahead of print]
Sadrai Z, Stevenson W, Okanobo A, Chen Y, Dohlman TH, Hua J, Amparo F, Chauhan SK, Dana R.
Schepens Eye Research Institute and Massachusetts Eye & Ear Infirmary, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts, 02114, United States.