Candidates against infection

Abstract

The present invention relates to the use of plasminogen/plasmin and its derivatives as agents for enhancing host defense against infection or other infectious diseases. The invention also relates to a method for screening of compounds which enhance host defense against infection by evaluating the host defense against bacterial arthritis and spontaneous otitis media in an animal model.

1 . A method for the prophylaxis, prevention and/or treatment of infectious disease, which comprises administering a pharmaceutical composition comprising an effective amount of a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , wherein the infectious disease is a bacterial infectious disease or a viral infectious disease. 
     
     
         3 . The method of  claim 2 , wherein the bacterial infectious disease is selected from the group consisting of otitis media and bacterial arthritis. 
     
     
         4 . The method of  claim 2 , wherein the bacterial infectious disease is selected from the group consisting of pneumonia, injuries in the respiratory organs caused by infections, and injuries in the joint tissues caused by infections. 
     
     
         5 . The method of  claim 2 , wherein the bacterial infectious disease is selected from the group consisting of gingivitis, periodontitis, and conjunctivitis. 
     
     
         6 . The method of  claim 1 , wherein the pharmaceutical composition comprises a combination of two or more of the compounds. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition further comprises at least one antibiotic agent. 
     
     
         8 . The method of  claim 7 , wherein the antibiotic agent is selected from the group consisting of tetracyclines, amphenicols, beta-lactams, penicillins, sulphonamides, macrolides, lincosamides, streptogamins, streptomycins, quinolones and metronidazoles. 
     
     
         9 . The method of  claim 1 , wherein the subject is a mammal. 
     
     
         10 . The method of  claim 1 , wherein the subject is deficient in plasmin or plasminogen. 
     
     
         11 . The method of  claim 10 , wherein the deficiency is selected from the group consisting of congenital, acquired, and local. 
     
     
         12 . The method of  claim 1 , wherein the pharmaceutical composition is administered by a method selected from the group consisting of systemically, locally, topically, intravenously, intramuscularly, subcutaneously, via inhalation, intrathecally, via local injection, via intra-articular injection, and per rectally. 
     
     
         13 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with a suitable polypeptide carrier or stabilizing agent. 
     
     
         14 . The method of  claim 1 , wherein the pharmaceutical composition is administered at a dose of 0.05 mg to about 10 mg. 
     
     
         15 . The method of  claim 1 , wherein the administration of the pharmaceutical composition is repeated at least once. 
     
     
         16 . The method of  claim 1 , wherein administering a pharmaceutical composition is performed by applying a wound dressing, comprising the pharmaceutical composition, to an infected area. 
     
     
         17 . The method of  claim 1 , wherein the method further comprises inducing an immune response against an infectious pathogen. 
     
     
         18 . A pharmaceutical composition for the prophylaxis, prevention and/or treatment of infectious disease comprising an effective amount of a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen. 
     
     
         19 . A kit of parts for use in the prophylaxis, prevention and/or treatment of infectious disease comprising an effective amount of a compound selected from the group consisting of plasminogen, Lys-plasminogen, Glu-plasminogen, variants of plasminogen comprising one or more of the kringle domains and the proteolytic domain, mini-plasminogen, and kringle domains of plasminogen and at least one antibiotic or antimycotic agent, in separate containers. 
     
     
         20 . The method of  claim 9 , wherein the mammal is a human. 
     
     
         21 . The method of  claim 14 , wherein the pharmaceutical composition is administered at a dose from about 0.5 to about 5 mg. 
     
     
         22 . The method of  claim 15 , wherein the administration of the pharmaceutical composition is repeated at least every day.