Pharmaceutical composition containing insulin-like growth factor-2 and use thereof

Abstract

Provided is the use of an insulin-like growth factor-2 for preparing a pharmaceutical composition, wherein the pharmaceutical composition is used for (i) promoting the expression of the macrophage PD-L1, and/or (ii) inhibiting the expression of the macrophage IL-10. Also provided is a pharmaceutical composition containing insulin-like growth factor-2 as an active ingredient.

1 . A method for (i) increasing PD-L1 expression in macrophage and/or (ii) inhibiting IL-1β expression in macrophages, comprising administering an effective amount of insulin-like growth factor-2 (IGF-2) to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the insulin-like growth factor-2 includes full length insulin-like growth factor-2 and an active fragment thereof. 
     
     
         3 . The method of  claim 2 , wherein the active fragment of insulin-like growth factor-2 has amino acids from position 25 to position 91 of insulin-like growth factor-2. 
     
     
         4 . The method of  claim 1 , wherein insulin-like growth factor-2 further:
 (a) promotes oxidative phosphorylation metabolic pathway in macrophages;   (b) promotes differentiation of regulatory T cell;   (c) inhibits differentiation of Th1 cell and/or Th17 cell; and/or   (d) treats an autoimmune disease.   
     
     
         5 . The method of  claim 4 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, inflammatory bowel disease, autoimmune encephalomyelitis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, insulin resistance, diabetes, liver cirrhosis and a combination thereof. 
     
     
         6 . A method for:
 (b) promoting differentiation of regulatory T cell;   (c) inhibiting differentiation of Th1 cell and/or Th17 cell; and/or   (d) treating an autoimmune disease   comprising administering an effective amount of macrophage treated with insulin-like growth factor-2 (IGF-2) to a subject in need thereof.   
     
     
         7 . A pharmaceutical composition comprising (a) insulin-like growth factor-2 or an active fragment thereof (such as active fragment having amino acids from position 25 to position 91), (b) macrophage scavenger, (c) optionally, PD-L1 agonist, and (d) a pharmaceutically acceptable carrier. 
     
     
         8 . (canceled) 
     
     
         9 . A pharmaceutical composition for regulating differentiation of T cell, comprising macrophage treated with insulin-like growth factor-2 and a pharmaceutically acceptable carrier. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the IGF-2 comprises an amino acid sequence of SEQ ID NO: 1. 
     
     
         12 . The method of  claim 1 , further comprising administering an effective amount of macrophage scavenger to a subject in need thereof, wherein the scavenger is a formulation for removing macrophage or inhibiting macrophage migration. 
     
     
         13 . The pharmaceutical composition of  claim 7 , wherein the macrophage scavenger is capable of depleting macrophage or suppressing macrophage migration. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the macrophage scavenger is selected from the group consisting of: CCR2 inhibitor, clodronate disodium liposome and a combination thereof.