Immunological and inflammatory pathogenesis of asthma: the predominance of ontogenic Th2 and its relation to developing immunological mechanisms during fetal and neonatal stages. Therapeutic implications
Villarrubia, V.; González, P.; Navarro, S.; Calvo, C.; de las Heras, M.; Alvarez-Mon, M.
Allergologia et Immunopathologia 27(4): 213-231
1999
ISSN/ISBN: 0301-0546 PMID: 10486445 Document Number: 506400
From an immunopathogenic vantage point, asthma appears to be a complex allergic/inflammatory disorder involving mechanism in which the specific immunological response shifts toward Th2 responses instead of Th1 responses. As a consequence of this shift, the cytokines IL-4, IL-5, IL-10, IL-13, TNF-alpha and CSF-GM are produced. The actions of these cytokines explain the phenomena of eosinophilic infiltration and mastocytic degranulation that characterize allergic asthma. The authors propose that the process of deviation toward Th2 responses occurs in the fetal stage and is a result of maternal immunological remodeling processes characteristics of pregnancy. In this period, the mother's mechanisms of immune rejection (mediated by Th1 lymphocytes and their cytokines IFN-gamma and IL-2) are detained or slowed, leading to the predominance of the Th-2 circuit. This predisposes the child to the development of an allergic response to a chance encounter with allergens, viruses and/or bacteria and/or parasites that activate the Th2 circuit. Moreover, deficits in the function of the Th1 circuit explain the sensitivity of the newborn to infections by viruses and other intracellular pathogens. Knowledge of these immunopathogenic mechanisms suggests that the future treatment of asthma and other allergic diseases will be based on the use of immunomodulators capable of stimulating Th1 response, thus achieving a) a god state of resistance to infection, and b) reductions of the production of pro-inflammatory cytokines. The experimental results of IL-12 in human beings with AM3 (an inductor of IFN-gamma and IL-12) support the pathogenic hypothesis proposed and open new ways for the treatment of asthma and other allergic diseases.