Light inhibitors for asthma, lung and airway inflammation, respiratory, interstitial, pulmonary and fibrotic disease treatment

Abstract

Methods of treating inflammatory conditions, disease and disorders are provided. Method include, for example, contacting or administering a sufficient amount of a LIGHT inhibitor to a subject to treat the inflammatory condition, disease or disorder.

What is claimed is: 
     
         1 . A method for reducing or inhibiting lung or airway inflammation, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject in need thereof to reduce or inhibit lung or airway inflammation in the subject. 
     
     
         2 . A method for reducing or inhibiting lung or airway inflammation, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject in need thereof to reduce or inhibit airway inflammation in the subject. 
     
     
         3 . A method for treating asthma, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject in need thereof to treat asthma. 
     
     
         4 . A method for treating a respiratory disease or disorder, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject in need thereof to treat the respiratory disease or disorder. 
     
     
         5 . A method for treating an interstitial or pulmonary disease or disorder, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject to treat the interstitial or pulmonary disease or disorder. 
     
     
         6 . A method for treating a fibrotic disease or disorder, comprising administering a sufficient amount of an inhibitor of LIGHT (p30 polypeptide) to a subject to treat the fibrotic disease or disorder. 
     
     
         7 . The method of  claim 4 , wherein the respiratory disease or disorder affects the upper or lower respiratory tract. 
     
     
         8 . The method of  claim 4 , wherein the respiratory disease or disorder comprises asthma, allergic asthma, bronchiolitis or pleuritis. 
     
     
         9 . The method of  claim 4 , wherein the respiratory disease comprises an allergic disorder. 
     
     
         10 . The method of  claim 9 , wherein the allergic disorder is selected from: Extrinsic bronchial asthma; Allergic rhinitis; Onchocercal dermatitis; Atopic dermatitis, Drug reactions; Nodules, eosinophilia, rheumatism, dermatitis, and swelling (NERDS); Eosophageal and a gastrointestinal allergy. 
     
     
         11 . The method of  claim 4 , wherein the respiratory disease or disorder is selected from: Airway Obstruction, Apnea, Asbestosis, Atelectasis, Berylliosis, Bronchiectasis, Bronchiolitis, Bronchiolitis Obliterans Organizing Pneumonia, Bronchitis, BronchopulmonaryDysplasia, Common Cold, Cough, Empyema, Pleural Empyema, Pleural Epiglottitis, Hemoptysis, Hypertension, Kartagener Syndrome, Meconium Aspiration, Pleural Effusion, Pleurisy, Pneumonia, Pneumothorax, Respiratory Distress Syndrome, Respiratory Hypersensitivity, Respiratory Tract Infections, Rhinoscleroma, Scimitar Syndrome, Severe Acute Respiratory Syndrome, Silicosis, Tracheal Stenosis, Whooping Cough and Influenza. 
     
     
         12 . The method of  claim 5 , wherein the interstitial or pulmonary disease or disorder, or the fibrotic disease or disorder, is selected from: Eosinophilic pleural effusions; Transient pulmonary eosinophilic infiltrates (Loffler); Histiocytosis; Chronic eosinophilic pneumonia; Hypersensitivity pneumonitis; Allergic bronchopulmonaryaspergillosis; Sarcoidosis; Idiopathic pulmonary fibrosis; pulmonary edema; pulmonary embolism; pulmonary emphysema; Pulmonary Hyperventilation; Pulmonary Alveolar Proteinosis; Chronic Obstructive Pulmonary Disease (COPD); Interstitial Lung Disease; and Topical eosinophilia. 
     
     
         13 . The method of any of  claims 1  to  12 , wherein treatment reduces, decreases, inhibits, delays, eliminates or prevents the probability, severity, frequency, or duration of one or more symptoms associated with or caused by the lung or airway inflammation, asthma or respiratory, interstitial, or pulmonary disease or disorder, or fibrotic disease or disorder. 
     
     
         14 . The method of any of  claims 1  to  12 , wherein one or more symptoms of the lung or airway inflammation, asthma or respiratory, interstitial, or pulmonary disease or disorder, or the fibrotic disease or disorder, is reduced, inhibited, abrogated, eliminated or reversed. 
     
     
         15 . The method of  claim 14 , wherein the symptom comprises shortness of breath (dyspnea), wheezing, stridor, coughing, airway remodeling, rapid breathing (tachypnea), prolonged expiration, runny nose, rapid or increased heart rate (tachycardia), rhonchous lung, over-inflation of the chest or chest-tightness, decreased lung capacity, an acute asthmatic episode, or lung, airway or respiratory mucosum inflammation or tissue damage. 
     
     
         16 . The method of  claim 14 , wherein the symptom comprises infiltration of eosinophils in lung, lung draining lymph nodes or airway, leukocyte infiltration of lung draining lymph nodes or airway, hyperplasia of mucus secreting epithelium, inflammatory lesion of lung, goblet cell hyperplasia, or increased Th2 cytokine production. 
     
     
         17 . The method of  claim 16 , wherein the Th2 cytokine is an interleukin (IL). 
     
     
         18 . The method of  claim 17 , wherein the interleukin (IL) comprises IL-4, IL-5, IL-9, IL-13, IL-16, IL-17 or IL-25. 
     
     
         19 . The method of any of  claims 1  to  12 , wherein the method reduces or inhibits progression, severity, frequency, duration or probability of a symptom of the lung or airway inflammation, asthma or respiratory, interstitial, or pulmonary disease or disorder, or fibrotic disease or disorder. 
     
     
         20 . The method of  claims 1  to  6 , wherein the lung or airway inflammation, asthma or respiratory, interstitial, or pulmonary disease or disorder, or fibrotic disease or disorder, is caused by an allergen or by exercise. 
     
     
         21 . The method of  claims 1  to  6 , wherein the lung or airway inflammation, asthma or respiratory, interstitial, or pulmonary disease or disorder, or fibrotic disease or disorder, is chronic or acute. 
     
     
         22 . A method for reducing or inhibiting a Th2-inflammatory response, comprising administering a sufficient amount of an inhibitor o LIGHT (p30 polypeptide) to a subject to reduce or inhibit Th2-inflammatory response. 
     
     
         23 . The method of  claim 22 , wherein the Th2-inflammatory response affects an organ or tissue of a subject. 
     
     
         24 . A method of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute asthmatic episode, comprising administering to a subject that has previously experienced an asthmatic episode or has been diagnosed as having asthma an amount of an inhibitor of LIGHT (p30 polypeptide) to reduce or decrease the probability, severity, frequency, duration or prevent an acute asthmatic episode. 
     
     
         25 . The method of  claim 24 , wherein the acute asthmatic episode is caused by or associated with allergic asthma. 
     
     
         26 . A method of increasing, enhancing or stimulating airway-dilation, comprising administering to a subject in need of increasing airway-dilation an amount of an inhibitor of LIGHT (p30 polypeptide) sufficient to increase, enhance or stimulate airway-dilation in the subject. 
     
     
         27 . A method of reducing or inhibiting airway-constriction, comprising administering to a subject in need thereof an amount of an inhibitor of LIGHT (p30 polypeptide) sufficient to reduce or inhibit airway-constriction in the subject. 
     
     
         28 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the inhibitor of LIGHT (p30 polypeptide) comprises an antibody or subsequence thereof that binds to LIGHT (p30 polypeptide), an antibody or subsequence thereof that binds to HVEM (herpesvirus entry mediator), or an antibody or subsequence thereof that binds to LTβR (lymphotoxin beta receptor). 
     
     
         29 . The method of  claim 28 , wherein the antibody is human or humanized. 
     
     
         30 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the inhibitor of LIGHT (p30 polypeptide) comprises an LTβR (lymphotoxin beta receptor), HVEM or LIGHT polypeptide subsequence, variant sequence, chimeric sequence or dominant negative sequence. 
     
     
         31 . The method of  claim 30 , wherein the chimeric sequence comprises a fusion of an LTβR or HVEM polypeptide sequence and an immunoglobulin sequence. 
     
     
         32 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the subject is a mammal. 
     
     
         33 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the subject is a human. 
     
     
         34 . The method of any of  claims 1  to  6 , wherein the method reduces or decreases undesirable or abnormal eosinophil migration, chemotaxis or generation. 
     
     
         35 . The method of any of  claims 1  to  6 , further comprising contacting or administering a second drug to the subject prior to, with or following administering the inhibitor of LIGHT (p30 polypeptide). 
     
     
         36 . The method of  claim 35 , wherein the second drug comprises an anti-inflammatory, anti-asthmatic or anti-allergy drug. 
     
     
         37 . The method of  claim 35 , wherein the second drug comprises a hormone or a steroid. 
     
     
         38 . The method of  claim 35 , wherein the second drug comprises an anti-histamine, anti-leukotriene, anti-IgE, anti-α4 integrin, anti-β2 integrin, anti-CCR3 antagonist, β2 agonist or anti-selectin. 
     
     
         39 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the inhibitor of LIGHT (p30 polypeptide) is administered via inhalation. 
     
     
         40 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the inhibitor of LIGHT (p30 polypeptide) is formulated into an aerosol. 
     
     
         41 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the subject is administered the inhibitor of LIGHT (p30 polypeptide) one, two, three, four or more times daily, weekly, monthly, bi-monthly, or annually. 
     
     
         42 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the amount of inhibitor of LIGHT (p30 polypeptide) administered is about 0.00001 mg/kg, to about 10,000 mg/kg, about 0.0001 mg/kg, to about 1000 mg/kg, about 0.001 mg/kg, to about 100 mg/kg, about 0.01 mg/kg, to about 10 mg/kg, about 0.1 mg/kg, to about 1 mg/kg body weight. 
     
     
         43 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the amount of the inhibitor of LIGHT (p30 polypeptide) administered to the subject is less than about 0.00001 mg/kg body weight. 
     
     
         44 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the amount is administered to the subject substantially contemporaneously with, or within about 1-60 minutes, hours, or days of the onset of a symptom associated with allergic asthma, an asthmatic episode or airway-constriction. 
     
     
         45 . The method of any of  claims 1  to  6 ,  22 ,  24 ,  26  and  27 , wherein the inhibitor of LIGHT (p30 polypeptide) is delivered to the lung or airways. 
     
     
         46 . A method of identifying an agent that reduces or inhibits lung or airway inflammation, comprising:
 a) administering a test inhibitor of LIGHT (p30 polypeptide) to a subject; and   b) measuring lung or airway inflammation in the subject, wherein a reduction or inhibition of lung or airway inflammation identifies the test inhibitor as an agent that reduces or inhibits lung or airway inflammation.   
     
     
         47 . A method of identifying an agent for treating asthma, comprising:
 a) administering a test inhibitor of LIGHT (p30 polypeptide) to a subject; and   b) measuring a symptom of asthma in the subject, wherein a reduction or inhibition of a symptom of asthma identifies the test inhibitor as an agent for treating asthma.   
     
     
         48 . A method of identifying an agent for treating fibrosis, comprising:
 a) administering a test inhibitor of LIGHT (p30 polypeptide) to a subject; and   b) measuring a symptom of fibrosis in the subject, wherein a reduction or inhibition of a symptom of fibrosis identifies the test inhibitor as an agent for treating fibrosis.