Methods and compositions for islet cell preservation

Abstract

Embodiments of the present invention illustrate methods of treating and preventing transplantation and side effects associated with transplantation. In particular, the present invention relates to compositions and methods for inhibition of graft rejection and promotion of graft survival. Thus, the invention relates to modulation of cellular activities, including graft rejection, promotion of graft survival, graft versus host rejection and conditions commonly associated with graft rejection. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease and inducers of other alpha 1-antitrypsin activities.

What is claimed: 
     
         1 . A method for preserving or modulating islet cell functions comprising, alpha 1-antitrypsin or peptide derivative thereof provided to an islet cell and preserving or modulating islet cell functions. 
     
     
         2 . The method of  claim 1 , wherein the composition is administered to a subject having Type 1 diabetes, wherein the composition preserves the subject's islet cell functions. 
     
     
         3 . The method of  claim 1 , wherein the composition is administered to a subject having Type 2 diabetes, wherein the composition preserves the subject islet cell functions. 
     
     
         4 . The method of  claim 1 , wherein the composition is administered to a subject undergoing an islet cell transplant or islet cell infusion. 
     
     
         5 . The method of  claim 1 , wherein the composition is administered to a subject having loss of islet cell function related to systemic or pancreatic inflammation. 
     
     
         6 . The method of  claim 1 , wherein preserving or modulating islet cell functions comprise preserving or modulating production of insulin; islet cell viability; inhibition of production, release, levels, half-life, activity or combination thereof of chemokines; inhibition of nitric oxide levels; and inhibition of inflammatory cytokine production, release, levels, half-life, activity or combination thereof. 
     
     
         7 . The method of  claim 6 , wherein modulating production of insulin comprises increasing production of insulin in islet cells. 
     
     
         8 . The method of  claim 6 , wherein modulating production of insulin comprises increasing secretion of insulin from islet cells. 
     
     
         9 . The method of  claim 1 , wherein a subject is administered the composition and the subject is a mammalian subject. 
     
     
         10 . The method of  claim 9 , wherein the mammalian subject is an adult or a juvenile. 
     
     
         11 . The method of  claim 1 , wherein the composition further comprises one or more anti-transplant rejection agents, anti-inflammatory agents, immunosuppressive agents, immunomodulatory agents, anti-microbial agents, or a combination thereof. 
     
     
         12 . The method of  claim 1 , wherein the composition comprises a composition of one or more carboxyterminal peptides derivative of alpha-1 antitrypsin. 
     
     
         13 . The method of  claim 6 , wherein inhibition of inflammatory cytokine production release, levels, half-life, activity or combination thereof comprises inhibition of TNFα (tumor necrosis factor alpha), IL-1 (interleukin-1α and interleukin-1β), IL-12 (interleukin-12), IL-17 (interleukin-17), IL-18 (interleukin-18), IL-23 (interleukin-23), IFNγ (interferon gamma) and a combination thereof. 
     
     
         14 . The method of  claim 6 , wherein the composition reduces the level of macrophage inflammatory protein 1 expressed by the islet cells. 
     
     
         15 . A method of treating a subject having compromised or reduced islet cell function compared to a control subject comprising administering to the subject a therapeutically effective amount of a composition comprising alpha 1-antitrypsin or peptide derivative thereof to the subject and improving islet cell functions compared to a control not having such a composition. 
     
     
         16 . The method of  claim 15 , wherein the subject has diabetes. 
     
     
         17 . The method of  claim 15 , wherein the subject is at risk of developing diabetes. 
     
     
         18 . The method of  claim 15 , wherein the subject has Type 1 diabetes. 
     
     
         19 . The method of  claim 15 , wherein the subject has Type 2 diabetes. 
     
     
         20 . The method of  claim 15 , wherein the composition comprises a composition of one or more carboxyterminal peptide derivatives of alpha-1 antitrypsin. 
     
     
         21 . The method of  claim 15 , further comprising one or more additional cytokine inhibitory agents. 
     
     
         22 . The method of  claim 21 , wherein the cytokine inhibitory agents further inhibit inflammatory cytokines. 
     
     
         23 . The method of  claim 22 , wherein the inflammatory cytokines comprise IL-1, TNFα or a combination thereof.