Immunomodulation as asthma therapy: where do we stand?
There is increasing evidence that chronic inflammation in asthma is mediated via a network of cytokines emanating from inflammatory and structural cells in the airways. The prominent eosinophilic inflammation that characterizes asthma appears to be orchestrated by cytokines derived from type 2 T-helper (Th2)-like lymphocytes, suggesting that immunosuppressants might be beneficial in the control of asthma. Indeed, one of the critical modes of action of glucocorticoids in controlling asthma may be the suppression of Th2-lymphocyte-derived cytokines, such as interleukin-5 (IL-5). Cyclosporin-A may have a similar immunomodulatory role, but its potential beneficial effects are outweighed by its toxicity, at least when given parenterally. Future immunomodulators need to be more selective, either by means of delivery (inhalation, liposomes) or by a more specific effect on Th2, as opposed to Th1, lymphocytes or their products. Such approaches may include new immunomodulators, such as mycophenolate mofetil, specific cytokine inhibitors (such as interleukin-5 antibodies), endogenous suppressors of Th2 cells (interferon-gamma or interleukin-12), or type 4 phosphodiesterase inhibitors.
Barnes
P J
PJ
Dept of Thoracic Medicine, National Heart and Lung Institute, London, UK.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D004205:Cromolyn Sodium / Q000009:adverse effects / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D006046:Gold / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018942:Macrolides; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D017835:Nedocromil / Q000009:adverse effects / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D013806:Theophylline / Q000009:adverse effects / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D001993:Bronchodilator Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018942:Macrolides; D010726:Phosphodiesterase Inhibitors; D017835:Nedocromil; D006046:Gold; D016572:Cyclosporine; D013806:Theophylline; D019001:Nitric Oxide Synthase; D004205:Cromolyn Sodium; D008727:Methotrexate