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.

Purpose:
To determine the effect of phosphodiesterase type-4 (PDE4) inhibition on IL17- associated immunity in experimental dry eye disease (DED).
 Methods:
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.
 Results:
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.
 Conclusions:
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.