Reversal of viral-induced systemic shock and respiratory distress by blockade of the lymphotoxin beta pathway

Abstract

This invention provides methods of inducing an antiviral response in an individual comprising administering to the individual an effective amount of a LT-B blocking agent and a pharmaceutically acceptable carrier. In particular this invention provides methods for treating viral-induced systemic shock and respiratory distress.

1 . A method of inducing an antiviral response in an individual suffering from viral-induced systemic shock and/or pulmonary distress, comprising administering to the individual an effective amount of a composition comprising a lymphotoxin-beta (LT-beta) blocking agent or a lymphotoxin-beta receptor (LT-beta-R) blocking agent, and a pharmaceutically acceptable carrier, such that an antiviral response is induced. 
   
   
       2 . The method of  claim 1 , wherein said LT-beta blocking agent is an anti-LT-beta-R antibody which binds LT-beta-R or soluble LT-beta-R. 
   
   
       3 . The method of  claim 2  wherein said agent is a LT-beta-R/immunoglobulin fusion (Ig fusion) protein. 
   
   
       4 . The method of  claim 1  wherein said LT-beta blocking agent is a soluble lymphotoxin-beta or an antibody against lymphotoxin-beta. 
   
   
       5 . The method of  claims 1 - 4  wherein said individual is infected with Sin Nombre Virus, Ebola virus, Marburg virus, Lassa virus or Dengue. 
   
   
       6 . The method of  claim 5  wherein the agent is a LT-beta-R/Ig fusion protein. 
   
   
       7 . A method of treating viral-induced systemic shock in an individual comprising administering to the individual an effective amount of a composition comprising a lymphotoxin-beta (LT-beta) or a lymphotoxin-beta receptor (LT-beta-R) blocking agent, and a pharmaceutically acceptable carrier, such that viral-induced systemic shock is treated. 
   
   
       8 . The method of  claim 7 , wherein the LT-beta blocking agent is an antibody against LT-beta or a soluble LT-beta. 
   
   
       9 . The method of  claim 7 , wherein the LT-beta-R blocking agent is an anti-LT-beta-R antibody which binds LT-beta-R or soluble LT-beta-R, or an LT-beta-R/immunoglobulin fusion (Ig fusion) protein. 
   
   
       10 . A method of treating viral infection in an individual suffering from viral-induced systemic shock and/or pulmonary distress, comprising administering to the individual an effective amount of a composition comprising a lymphotoxin-beta (LT-beta) blocking agent or a lymphotoxin-beta receptor (LT-beta-R) blocking agent and a pharmaceutically acceptable carrier, such that treatment occurs. 
   
   
       11 . The method of  claim 10 , wherein the LT-beta blocking agent is an antibody against LT-beta or a soluble LT-beta. 
   
   
       12 . The method of  claim 10 , wherein the LT-beta-R blocking agent is an anti-LT-beta-R antibody which binds LT-beta-R or soluble LT-beta-R, or an LT-beta-R/immunoglobulin fusion (Ig fusion) protein. 
   
   
       13 . A method of treating viral-induced pulmonary distress in an individual comprising administering to the individual an effective amount of a composition comprising a lymphotoxin-beta (LT-beta) blocking agent or a lymphotoxin-beta-receptor (LT-beta-R) blocking agent and a pharmaceutically acceptable carrier, such that viral-induced pulmonary distress is treated. 
   
   
       14 . The method of  claim 13 , wherein the LT-beta blocking agent is an antibody against LT-beta or a soluble LT-beta. 
   
   
       15 . The method of  claim 13 , wherein the LT-beta-R blocking agent is an anti-LT-beta R antibody which binds LT-beta-R or soluble LT-beta-R, or an LT-beta-R/immunoglobulin fusion (Ig fusion) protein.