Use of Apoptosis-specific eIF-5A siRNA to Down Regulate Expression of Proinflammatory Cytokines to Treat Sepsis

Abstract

The present invention relates to apoptosis specific eucaryotic initiation factor 5A (eIF-5A), referred to as apoptosis-specific eIF-5A or eIF5-A1, nucleic acids and polypeptides and methods for down regulating pro-inflammatory cytokines in a mammal by administering siRNA against eIF-5A1 to the mammal to treat/prevent sepsis and/or hemorrhagic shock.

1 . A method for decreasing expression of pro-inflammatory cytokines in vivo in a subject, comprising administering eIF5A1 siRNA to the subject, whereby the eIF5A1 siRNA decreases expression of pro-inflammatory cytokines in the subject. 
     
     
         2 . The method of  claim 1  wherein the subject is a human. 
     
     
         3 . The method of  claim 1  wherein the pro-inflammatory cytokine is selected from the group consisting of IL-1β, IL-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, IL-3, IL-6, IL-12(p40), IL-12(p70), G-CSF, KC, MIP-1α, and RANTES. 
     
     
         4 . The method of  claim 1  wherein the pro-inflammatory cytokine is TNF-α. 
     
     
         5 . The method of  claim 1  wherein the pro-inflammatory cytokine is IL-6. 
     
     
         6 . The method of  claim 1  wherein the pro-inflammatory cytokine is KC. 
     
     
         7 . The method of  claim 1  wherein the pro-inflammatory cytokine is MIP-1α. 
     
     
         8 . The method of  claim 1  wherein said decreased expression of pro-inflammatory cytokines further provides treatment of sepsis. 
     
     
         9 . The method of  claim 1  wherein the sense strand of the eIF5A1 siRNA comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29 and SEQ ID NO:32. 
     
     
         10 . A pharmaceutical composition for decreasing expression of pro-inflammatory cytokines, comprising eIF5A siRNA and a pharmaceutically acceptable carrier. 
     
     
         11 . The composition of  claim 11  wherein the sense strand of the siRNA comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29 and SEQ ID NO:32. 
     
     
         12 . A method of preventing hemorrhagic shock in a subject comprising administering an eIF5A1 siRNA or eIFA1 antisense polynucleotide to decrease expression of IL-1β and/or TNF-α in the subject, thereby preventing hemorrhagic shock. 
     
     
         13 . The method of  claim 1  wherein the sense strand of siRNA comprises SEQ ID NO: 30 and the antisense strand comprises SEQ ID NO: 31.