Treating Auto-Immune and Auto-Inflammatory Diseases

Abstract

The present invention relates to the formulations, methods and kits for reducing cytokine interleukin-17 (IL-17 or IL-17A) levels in both broncheoalveolar lavage fluid (BALF) and blood/serum and/or for the inhibition of p38 mitogen activating protein kinase (MAPK) activity involving the use of 17α-hydroxyprogesterone caproate (17-OHPC) or derivatives thereof. The formulation may be in the form of an inhalant containing effective amounts of 17-OHPC, and the formulation may be used in a method to treat IL-17 cytokine and/or p38 MAPK mediated auto-immune and auto-inflammatory diseases. Such diseases may include glucocorticoid (GC) insensitive related diseases or conditions. In alternate embodiment, the formulation may include the combined use of budesonide (BUD) with 17-OPHC.

1 - 20 . (canceled) 
     
     
         21 . A method for reducing vascular endothelial growth factor (VEGF) expression in a patient, comprising administering to said patient a pharmaceutical composition comprising an effective amount of progesterone or a derivative thereof. 
     
     
         22 . The method of  claim 21 , wherein the progesterone derivative is selected from the group consisting of 17-alpha-hydroxyprogesterone caproate (17-OHPC), 17-alpha-hydroxyprogesterone acetate and 17-alpha hydroxyprogesterone valproate. 
     
     
         23 . The method of  claim 22 , wherein the progesterone derivative is 17-OHPC. 
     
     
         24 . The method of  claim 21 , further comprising administering a second treatment agent comprising a glucocorticoid steroid to the subject. 
     
     
         25 . The method of  claim 24 , wherein the second treatment agent is administered before, coincident, or after the administering of the first treatment agent. 
     
     
         26 . The method of  claim 24 , wherein said glucocorticoid comprises budesonide (BUD). 
     
     
         27 . The method of  claim 21 , wherein said administering comprises inhalation. 
     
     
         28 . The method of  claim 23 , wherein the 17-OHPC comprises an amount of from 0.03 mg/L to 0.3 mg/L. 
     
     
         29 . The method of  claim 26 , wherein the BUD comprises 0.2 g/L. 
     
     
         30 . The method of  claim 21 , wherein the patient exhibits symptoms of glucocorticoid insensitivity that is associated with said disease. 
     
     
         31 . A method of reducing Matrix Metalloproteinase 9 (MMP9) expression in a patient, comprising administering to said patient a pharmaceutical composition comprising an effective amount of progesterone or a derivative thereof. 
     
     
         32 . The method of  claim 31 , wherein the progesterone derivative is selected from the group consisting of 17-alpha-hydroxyprogesterone caproate (17-OHPC), 17-alpha-hydroxyprogesterone acetate and 17-alpha hydroxyprogesterone valproate. 
     
     
         33 . The method of  claim 32 , wherein the progesterone derivative is 17-OHPC. 
     
     
         34 . The method of  claim 31 , further comprising administering a second treatment agent comprising a glucocorticoid steroid. 
     
     
         35 . The method of  claim 31 , wherein the second treatment agent is administered before, coincident, or after the administering of the first treatment agent. 
     
     
         36 . The method of  claim 34 , wherein said glucocorticoid comprises budesonide (BUD). 
     
     
         37 . The method of  claim 31 , wherein said administering comprises inhalation. 
     
     
         38 . The method of  claim 33 , wherein the 17-OHPC is administered in an amount of from 0.03 mg/L to 0.3 mg/L. 
     
     
         39 . The method of  claim 36 , wherein the second treatment agent comprises BUD at 0.2 g/L. 
     
     
         40 . The method of  claim 31 , wherein the MMP9 expression is reduced in the subject in both broncheoalveolar lavage fluid (BALF) and lung tissue.