Method of attenuating reactions to skin irritants

Abstract

The present invention is directed to a method of inhibiting CD1d activation by administering a composition containing a moiety that blocks CD1d activation. Compositions of the invention are useful for the attenuation of CD1d-restricted immune responses, including treatment of skin disorders due to hyperactive immune responses (e.g., contact hypersensitivity), for systemic administration to attenuate ongoing immune responses, and to provide hypoallergenic cosmetic products including pharmaceutical, cosmetic, and skin care compositions. Preferably, these compositions are in a form intended for topical administration.

1 . A composition comprising:
 (a) an agent that attenuates CD1d-restricted NK T cell responses, wherein the agent comprises an antagonist that binds CD1d and inhibits activation of CD1d-restricted NK T cells, agents that block CD1d-specific receptors, or CD1d decoys; and   (b) a pharmaceutically acceptable carrier or diluent for systemic administration.   
     
     
         2 . The composition of  claim 1 , wherein the agent is a glycolipid, a ceramide, or a phospholipid. 
     
     
         3 . The composition of  claim 2 , wherein the glycolipid is a monoglycosylated or diglycosylated ceramide. 
     
     
         4 . The composition of  claim 3 , wherein the monoglycosylated ceramide is αMan Cer or βGal Cer. 
     
     
         5 . The composition of  claim 2 , wherein the phospholipid is 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine (DPPE), 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly (ethylene glycol) 2000] (DPPE-PEG), or phophotidyl inositol. 
     
     
         6 . The composition of  claim 1 , wherein the agent is an antibody. 
     
     
         7 . The composition of  claim 1 , wherein systemic administration comprises oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intra-arterial injection, intrathecal administration, intra-peritoneal administration, sublingual administration, rectal administration, pulmonary administration, or intranasal administration. 
     
     
         8 . The composition of  claim 1 , wherein systemic administration is pulmonary administration or intranasal administration. 
     
     
         9 . The composition of  claim 1 , wherein the agent is an antibody, and wherein systemic administration is intravenous injection, subcutaneous injection, intramuscular injection, intra-arterial injection, intrathecal administration, or intra-peritoneal administration. 
     
     
         10 . The composition of  claim 1 , wherein the composition is useful for the treatment of allergic dermatitis, irritant dermatitis, contact dermatitis, and further eczematous dermatitises, atopical dermatitis, seborrheic dermatitis, Lichen planus,  Pemphigus , bullous Pemphigoid, epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinphilias, Lupus erythematosus, Alopecia areata, psoriasis, lupus, or spontaneous abortions. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . A composition comprising:
 (a) an agent that attenuates CD1d-restricted NK T cell responses, wherein the agent comprises antagonists that bind CD1d and inhibit activation of CD1d-restricted NK T cells or agents that block CD1d-specific receptors, wherein the agent is a phospholipid; and   (b) a pharmaceutically acceptable carrier or diluent for topical administration.   
     
     
         18 . (canceled) 
     
     
         19 . The composition of  claim 17 , wherein the agent is present in an amount no greater than 10.0% weight per volume. 
     
     
         20 . The composition of  claim 17 , wherein the phospholipid is 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine (DPPE), 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine-N-[Poly (ethylene glycol) 2000] (DPPE-PEG), or phophotidyl inositol. 
     
     
         21 . The composition of  claim 17 , wherein the composition is useful for the treatment of allergic dermatitis, irritant dermatitis, contact dermatitis, and further eczematous dermatitises, eczema, atopical dermatitis, seborrheic dermatitis, Lichen planus,  Pemphigus , bullous Pemphigoid, epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinphilias, Lupus erythematosus, Alopecia areata, or psoriasis. 
     
     
         22 . A composition comprising:
 (a) an agent that attenuates CD1d-restricted NK T cell responses, wherein the agent comprises an antagonist that binds CD1d and inhibits activation of CD1d-restricted NK T cells or agents that block CD1d-specific receptors, wherein the agent is an active agent, and wherein the agent is a glycolipid; and   (b) a pharmaceutically acceptable carrier or diluent for topical administration.   
     
     
         23 . The composition of  claim 22 , wherein the agent is present in an amount greater than 1.0% weight per volume. 
     
     
         24 . The composition of  claim 22 , wherein the glycolipid is a monoglycosylated or diglycosylated ceramide. 
     
     
         25 . The composition of  claim 24 , wherein the monoglycosylated ceramide is αMan Cer or βGal Cer. 
     
     
         26 . The composition of  claim 22 , wherein the composition is useful for the treatment of allergic dermatitis, irritant dermatitis, contact dermatitis, and further eczematous dermatitises, eczema, seborrheic dermatitis, Lichen planus,  Pemphigus , bullous Pemphigoid, epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinphilias, Lupus erythematosus, Alopecia areata, or psoriasis. 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled)