Use of inhibitors of il-36 proteolytic processing for the treatment and/or reduction of inflammation

Abstract

This invention relates to the use of an agent capable of inhibiting IL-36 proteolytic processing for the treatment and/or reduction of inflammation in a subject. Advantageously, the agent prevents the production of a biologically active IL-36 to prevent and/or reduce the pro-inflammatory effects of IL-36. The invention also relates to a method for treatment and/or reduction of inflammation and compositions for treating and/or reducing inflammation.

1 . A method for the treatment of inflammatory skin disorders in a subject in need thereof, the method comprising administering to the subject an effective amount of a serine protease inhibitor or a cysteine protease inhibitor capable of inhibiting IL-36 activation that occurs via proteolytic processing, including IL-36α, IL-36β, or IL-36γ activation, and a combination thereof, wherein the serine protease inhibitor or cysteine protease inhibitor prevents and/or inhibits the activity of IL-36 activating proteases or activators thereof. 
     
     
         2 . The method according to  claim 1 , wherein the serine protease inhibitor or cysteine protease inhibitor is a small molecule, peptide, polypeptide, protein, siRNA, sgRNA, antibody, or a combination thereof. 
     
     
         3 . The method according to  claim 1 , wherein the inflammatory skin disorder is selected from plaque psoriasis, guttate psoriasis, palmoplantar psoriasis, generalized pustular psoriasis, flexural psoriasis, inverse psoriasis, erythrodermic psoriasis, psoriasis vulgaris, arthritic psoriasis, eczema, granuloma annulare, lichen planus, bullous pemphigoid, molluscum contagiosum, dermatomyositis and ichthyosis vulgaris, dermatitis, and acne. 
     
     
         4 . The method according to  claim 1 , wherein the IL-36 activating protease or activator thereof is selected from the group consisting of elastase, cathepsin G, cathepsin K, proteinase-3 and DPPI (Cathepsin C). 
     
     
         5 . The method according to  claim 1 , wherein the serine protease inhibitor or cysteine protease inhibitor is selected from cathepsin K inhibitor, cathepsin C(DPPI) inhibitor, an elastase inhibitor, cathepsin-G inhibitor or proteinase-3 inhibitor selected from Boswellic Acids, cathepsin G inhibitor I, Elastase inhibitor IV, Sodium Fluoride, 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF.HCl), phenylmethanesulfonylfluoride (PMSF), odanacatib, balicatib and MV061194. 
     
     
         6 . The method according to  claim 1 , wherein the serine protease inhibitor or cysteine protease inhibitor is a polyclonal or monoclonal antibody raised against at least one neutrophil-derived protease, wherein the antibody binds to the protease to prevent its binding to at least one protease cleavage site within IL-36 required for activation of IL-36. 
     
     
         7 . The method according to  claim 1 , wherein the serine protease inhibitor or cysteine protease inhibitor is a polyclonal or monoclonal antibody raised against at least one of the proteases elastase or cathepsin G or cathepsin K. 
     
     
         8 . A composition for treatment of an inflammatory skin disorder, the composition comprising an agent capable of inhibiting IL-36 activation via proteolytic processing, and a suitable pharmaceutical excipient.