Suppression of acute uveitis following treatment with repository corticotropin injection

Abstract Repository corticotropin injection (RCI: H.P. Acthar® gel) contains a purified porcine pituitary ACTH-analogue, and is an FDA-approved treatment for several inflammatory eye diseases. ACTH binds to all 5 known melanocortin receptors and may suppress inflammation by steroid-dependent and independent pathways. Endotoxin-induced uveitis (EIU) in rodents is a useful experimental model to investigate mechanism of action and pharmacological efficacy of potential treatments. This study was conducted to investigate the potential anti-inflammatory benefit of RCI in an acute rat model of EIU. EIU is characterized by clinically relevant signs of inflammation, including inflammatory cytokines and cells in the anterior and vitreous chambers. Rats (n=16 group) were treated with dexamethasone (Dex), placebo, or RCI at 160 IU/kg, 400 IU/kg or 800 IU/kg following EIU induction. Eyes were clinically examined at pre-challenge, 6–8, 24, and 48 hours post LPS challenge using the Combined Draize and McDonald – Shadduck Scoring System. Treatment Group Ocular Clinical Score (mean ± sem) IL-1a (pg/ml) (mean ± sem) MIP2a (pg/ml) (mean ± sem) Placebo 15.5 ± 1.2 207.1 ± 68.9 240 ± 47 Acthar 160 IU/kg 9.4 ± 1.0 130.3 ± 34.6 158 ± 43 Acthar 400IU/kg 2.0 ± 0.3* 95.7 ± 20.3 114 ± 18* Acthar 800 IU/kg 0.9 ± 0.2* 50.9 ± 8.3* 126 ± 32* Dex 2.6 ± 0.5* 54.4 ± 10.5* 92 ± 10* *= p ≤ 0.01 We show that RCI treatment significantly reduced ocular inflammation and inflammatory cytokines in an EIU model of acute uveitis. RCI has the potential opportunity to be therapeutic for a wide range of inflammatory and autoimmune diseases, including uveitis. The mechanism of action of RCI may involve more than the induction of corticosteroids, and will be explored further in future studies.