Contributing factors to the pathobiology of asthma. The Th1/Th2 paradigm.
CD4+ "helper" T-lymphocytes in murine and human models have been divided into Th1 and Th2 subclasses, characterized by the profile of cytokines they secrete: INF-gamma (and perhaps IL-2 and TNF-beta) by Th1 cells, and IL-4 (and perhaps IL-5, IL-6, IL-10, and IL-13) by Th2 cells. Although a strict division into Th1 and Th2 phenotypes in humans (unlike murine systems) may not be possible, the asthmatic diathesis in humans appears to be one largely characterized by inflammatory responses associated with Th2 cells and their cytokines, particularly IL-4, IL-13, and IL-5. Other pulmonary disorders, such as those associated with infectious diseases including tuberculosis, appear to favor an immunologic response characteristic of Th1-cells, and its defining cytokine IFN-gamma. This apparent Th1/Th2 immune dysregulation in asthma is an area of active investigation and forms the basis for ongoing attempts to change this phenotype through a variety of approaches. These include immunotherapy with conventional antigens, designer peptides, oligonucleotides, and anti-IgE, and pharmacotherapy with immune modulating drugs, cytokines, cytokine agonists and cytokine antagonists, and antibodies. This field of investigation promises to usher in a whole new approach to our understanding of asthma and ways to approach its treatment.
Colavita
A M
AM
Division of Critical Care, Pulmonary, Allergic and Immunologic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Reinach
A J
AJ
Peters
S P
SP
D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007378:Interleukins / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*
D016207:Cytokines; D007378:Interleukins