Growth factors

In chronic tissue injury, it appears the process of repair loses many of the control mechanisms, and continued repair results in remodeling of the tissue with alteration of normal structure and compromise of normal lung function. A large number of studies have investigated the role of growth factors in human lung disease in which tissue remodeling is a prominent feature. The remodeling process involves excess matrix synthesis along with distorted deposition of that matrix; in addition there is the appearance of altered tissue cell phenotypes, most notably that of the myofibroblast. However, there may be situations involving structural cell phenotype or extra cellular matrix alterations that can propagate the remodeling process through autocrine and paracrine pathways independent of the state of inflammation that may have preceded the alteration. In asthma, TNF- can amplify the inflammatory process and have indirect influence on airway remodeling through induction of other growth factors. It has been detected in BAL fluid of asthmatics, in alveolar macrophages after allergen challenge and in bronchial mucosa of asthma patients and can be rapidly released from mast cells on degranulation. Of the many cytokines and growth factors that are found within the tissue or surrounding fluids in COPD and asthma, only a few can be shown to have direct impact on the process of tissue remodeling. In vitro and in vivo studies outlined above indicate that factors such as TGF-, which induces chronic repair without accompanying tissue injury, and IL-1 , which induces tissue injury and chronic repair, likely through induction of TGF-, may be considered the most critical targets for intervention.