PREVENTION AND TREATMENT OF INFLAMMATORY CONDITIONS
In accordance with some embodiments herein, methods and compositions for prevention and treatment of inflammatory conditions are provided. In some embodiments, compositions comprising NKT-2 activators, for example miltefosine are provided. In some embodiments, the compositions further comprise sulfatide and/or a RAR agonist. In some embodiments, the compositions comprise activators of Type II NKT cells, and/or inhibitors of Type I NKT cells.
1 .- 115 . (canceled)
116 . A method for alleviating or preventing at least one inflammatory condition in a subject comprising administering an amount of an NKT-2 activator sufficient to activate type II NKT cells to the subject.
117 . The method of claim 116 wherein the inflammatory condition is selected from the group consisting of: fatty liver disease, alcohol induced hepatitis, non-alcoholic steatosis hepatitis, autoimmune hepatitis, cirrhosis, non-alcoholic fatty liver disease, fibrosis, primary sclerosing cholangitis, primary biliary sclerosis, fulminating cirrhosis, idiopathic hepatitis, viral-induced hepatitis (A, B, C and other), inflammatory hepatitis associated with hepato-biliary carcinoma, multiple sclerosis, type 1 diabetes, ischemic reperfusion injury, solid organ transplantation, systemic lupus erythematosus, rheumatoid arthritis, amyotrophic lateral sclerosis, and inflammatory bowel disease (Crohn's and colitis).
118 . The method of claim 116 , further comprising administering to the subject an amount of a RAR agonist sufficient to inhibit activation of type I NKT cells to the subject.
119 . The method of claim 118 wherein the NKT-2 activator and the RAR agonist are administered simultaneously.
120 . The method of claim 118 , wherein the NKT-2 activator and RAR agonist are administered separately.
121 . The method of claim 116 , wherein the NKT-2 activator comprises at least one of miltefosine, a miltefosine analog, or a phospholipid.
122 . The method of claim 121 , wherein the phospholipid comprises lysophophatidylcholine (LPC), an analog of LPC, lyso platelet-activating factor (LPAF), a lysosphingomyelin (LSM), or an analog of LSM.
123 . The method of claim 116 , wherein the NKT-2 activator comprises at least one of miltefosine or a miltefosine analog.
124 . The method of claim 123 , wherein the miltefosine analog comprises a compound from Table 2.1 or Table 2.2.
125 . The method of claim 116 , wherein the NKT-2 activator comprises miltefosine.
126 . The method of claim 118 , wherein the RAR agonist comprises tazarotene.
127 . The method of claim 118 , wherein the NKT-2 activator comprises miltefosine.
128 . The method of claim 116 , wherein the amount of NKT-2 activator is sufficient to activate CD8αα + T cells in the liver of the subject.
129 . The method of claim 116 , further comprising administering isolated CD8αα + , TCRαβ + T cells to the subject.
130 . A method for alleviating or preventing at least one inflammatory condition in a subject comprising administering an amount of NKT-2 activator and an amount of sulfatide to the subject, wherein the amount of an NKT-2 activator and the amount of sulfatide together are sufficient to activate type II NKT cells in the subject.
131 . The method of claim 130 wherein the inflammatory condition is selected from the group consisting of: fatty liver disease, alcohol induced hepatitis, non-alcoholic steatosis hepatitis, autoimmune hepatitis, cirrhosis, non-alcoholic fatty liver disease, fibrosis, primary sclerosing cholangitis, primary biliary sclerosis, fulminating cirrhosis, idiopathic hepatitis, viral-induced hepatitis (A, B, C and other), inflammatory hepatitis associated with hepato-biliary carcinoma, multiple sclerosis, type 1 diabetes, ischemic reperfusion injury, solid organ transplantation, systemic lupus erythematosus, rheumatoid arthritis, amyotrophic lateral sclerosis, and inflammatory bowel disease (Crohn's and colitis).
132 . The method of claim 130 , wherein the amount of NKT-2 activator is sufficient to activate type II NKT cells in the subject, and the amount of sulfatide is sufficient to activate type II NKT cells in the subject.
133 . The method of claim 130 , further comprising administering to the subject an amount of a RAR agonist sufficient to inhibit activation of type I NKT cells to the subject.
134 . A composition for use in alleviating or preventing at least one inflammatory condition in a subject, the composition comprising an amount of a NKT-2 activator sufficient to activate type II NKT cells in the subject.
135 . The composition of claim 134 further comprising an amount of a RAR agonist sufficient to inhibit activation of type I NKT cells to the subject.