Macrophage activation, chronic inflammation and gastrointestinal disease.

The involvement of macrophages in chronic inflammatory conditions has been the subject of considerable experimental investigation in recent years. Macrophages are able to secrete a wide range of biologically active compounds. They are important in the control of infection and, through their immunological and non-immunological receptors, macrophages interact with other cell types and a wide variety of proteins. Monocyte proliferation is apparent in a number of disorders, including collagen diseases, many infectious diseases, neo-plastic conditions and chronic inflammatory gastrointestinal diseases.' Generalised proliferation of mature macrophages is present in chronic granulomatous conditions such as tuberculosis, brucellosis and other infections by obligate intracellular parasites as well as in berylliosis and sarcoidosis. Other examples of macrophage proliferation include storage diseases for example, Gaucher's disease, neoplastic macrophage proliferation and monocyte-macrophage dysfunction syndromes. The latter syndromes include chronic granulomatous disease2 and various lymphoproliferative disorders.3 Macrophage dysfunction may also result from adrenocorticosteroid administration or exposure to ionising radiation.' Macrophage cell function has been extensively investigated in disorders such as lepromatous leprosy, miliary tuberculosis, disseminated fungal infections and in Hodgkin's disease. Intrinsic or acquired functional defects, however, have not been convincingly proved in these conditions.4 Recent information on the tissue damaging potential of compounds released from activated macrophages has focused interest on a wide variety of chronic inflammatory conditions where macrophages may potentiate tissue damage in a non-specific manner.5 Early work in this area concentrated on rheumatic diseases where the results strongly supported the concept of macrophage protease involvement in the promotion of inflammation.6 These ideas have been more recently extended to various alimentary conditions,7-' including acute or chronic liver disease and inflammatory bowel disease. The purpose of this review is to highlight recent advances concerning macrophage function, kinetics, activation, and heterogeneity and to consider how far macrophages may be involved in the promotion of inflammation in a variety of gastrointestinal diseases. General information will be presented, followed by a detailed review of the literature relevant to alimentary disease.