Calcium Flux Agonists And Methods Therefor

Abstract

Calcium flux agonists are used to enhance a TLR- or NOD-mediated stimulus and to so increase an immune response of a host and reduce healing time. Preferred calcium flux agonists include Ca 2+ ionophores and SERCA inhibitors and are used in synergistic quantities where a ligand to a TLR or NOD receptor is present.

1 . A pharmaceutical composition comprising:
 a calcium flux agonist in a pharmaceutically acceptable carrier,   wherein the pharmaceutical composition is formulated for topical application to injured or infected skin; and   wherein the calcium flux agonist is present in an amount that enhances, upon application of the formulation to the injured or infected skin, an immune response of an immune competent cell in the injured or infected skin to a ligand of a pattern recognition receptor.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the calcium flux agonist is a calcium ionophore or a SERCA inhibitor. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the pattern recognition receptor is a TLR receptor or a NOD receptor. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for topical application to injured or infected skin via a solid carrier that is applied to the injured or infected skin. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the amount of calcium flux agonist synergistically enhances the immune response in the presence of the ligand as compared to the immune response in the absence of the ligand. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the calcium flux agonist is ionomycin, calcimycin, 2,5-di-tert-butylhydro-quinone (DBHQ), or thapsigargin. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the skin is infected with a bacterial pathogen that comprises a ligand for a TLR receptor or a NOD receptor. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the calcium flux agonist is a calcium ionophore. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the calcium ionophore is ionomycin, calcimycin, calcium ionophore II, calcium ionophore IV, calcium ionophore V, or calcium ionophore VI. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the calcium flux agonist is a SERCA inhibitor. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the SERCA inhibitor is 2,5-Di-tert-butylhydroquinone, thapsigargin, ruthenium red, gingerol, paxilline, or cyclopiazonic acid. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for topical application to injured or infected skin, either prophylactically prior to surgery or other manipulation, or therapeutically.