Oral treatment of inflammatory bowel disease

Abstract

The present invention relates to treatment of an inflammatory bowel disease by simultaneous or successive parental and oral administration of a mammalian beta defensin.

What is claimed is: 
     
         1 . A method of treatment of an inflammatory bowel disease, the method comprising simultaneous or successive oral and parenteral administration of a therapeutically effective amount of one or more mammalian beta defensins to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the one or more defensins are administered orally after at least one occasion of parenteral administration of one or more defensins. 
     
     
         3 . The method of  claim 1 , wherein the one or more defensins are administered orally together with at least one parenteral administration of a dosage of one or more defensins. 
     
     
         4 . A method of keeping a subject suffering from an inflammatory bowel disease in remission or prolonging remission, the method comprising oral administration of a therapeutically effective amount of one or more mammalian beta defensins to the subject. 
     
     
         5 . The method of  claim 1 , wherein the subject suffers from Crohn's disease. 
     
     
         6 . The method of  claim 1 , wherein the subject suffers from mild active disease or moderately to severely active disease. 
     
     
         7 . The method of  claim 1 , wherein the subject suffers from ulcerative collitis. 
     
     
         8 . The method of  claim 7 , wherein the colitis is a pancolitis or left sided colitis. 
     
     
         9 . The method of  claim 1 , wherein the subject is human and the one or more mammalian beta defensins are one or more human beta defensins. 
     
     
         10 . The method of  claim 1 , wherein the one or more mammalian beta defensins comprise an amino acid sequence having at least 80% sequence identity to any one of the amino acid sequences selected from the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, and SEQ ID NO 4. 
     
     
         11 . The method of  claim 1 , wherein the one or more mammalian beta defensins comprise an amino acid sequence having at least 80% sequence identity to SEQ ID NO 2. 
     
     
         12 . The method of  claim 1 , wherein the one or more mammalian beta defensins comprise a variant of human beta defensin 2, wherein no more than 10 amino acids have been changed compared to SEQ ID NO 2. 
     
     
         13 . The method of  claim 1 , wherein the one or more mammalian beta defensins are capable of downregulating the activity of at least one pro-inflammatory cytokine in a human cell selected from the group consisting of human PBMCs, human CD14+ monocyte-derived dendritic cells, a human monocyte cell line, and human immature dendritic cells. 
     
     
         14 . The method of  claim 13 , wherein the proinflammatory cytokine is selected from the group consisting of TNFα, IL-23, and IL-1β. 
     
     
         15 . The method of  claim 1 , wherein the one or more mammalian beta defensins are capable of up-regulating the activity of at least one anti-inflammatory cytokine in a human cell selected from the group consisting of human PBMCs, human CD14+ monocyte-derived dendritic cells, a human monocyte cell line, and human immature dendritic cells. 
     
     
         16 . The method of  claim 15 , wherein the anti-inflammatory cytokine is IL-10. 
     
     
         17 . The method of any of  claim 1 , wherein the one or more mammalian beta defensins are administered at least once daily. 
     
     
         18 . The method of any of  claim 1 , wherein the one or more mammalian beta defensins are administered at a daily dosage of from about 0.0001-10 mg/kg. 
     
     
         19 . The method of  claim 1 , wherein a defensin is administered orally and a defensin is administered parenterally and the orally administered defensin and parenterally administered defensin are the same. 
     
     
         20 . The method of  claim 1 , wherein a defensin is administered orally and a defensin is administered parenterally and the orally administered defensin and parenterally administered defensin are different.