Macrophages and allergic lung disease.

Allergic lung diseases such as atopic asthma and extrinsic allergic alveolitis are now recognized as chronic inflammatory lung diseases promoted by dysregulation of T cell-mediated immune mechanisms. The basis of this regulation and the impact of the atopic status of these individuals on this chronic inflammatory disease have yet to be fully explained. The studies described in this paper reveal mechanisms of macrophage lymphocyte interaction in which evidence is presented that a balance of functionally distinct macrophage subsets needs to be maintained to regulate T cell reactivity in the lung. Similarly a balance within the T cell populations may influence and regulate the relative proportions of functionally distinct macrophages. Investigations of bronchoalveolar lavage and biopsy from patients with allergic lung disease have revealed a gross imbalance within the lung macrophage populations and an associated dysregulation in T cell stimulation. In vitro studies have revealed that imbalances in the macrophage populations may lead to changes in local level of cytokine production specifically TGF-beta which would then impact on the control of T cell populations. Conversely aberrant development of activated T cells with a TH2-like cytokine repertoire may influence the balance of macrophages. Our in vitro studies have revealed that macrophage phenotype and function can be modulated in vitro by contact with T cell-derived cytokines and that this change in phenotype is reflected in a change in function. These data support the hypothesis that components of the immune system normally associated with allergic reactions may be stimulated in the absence of any overt atopic reactivity in the individual concerned. Thus immediate type allergic reactions may represent a "super-imposed" burden [provocating factor] in atopic individuals but the underlying immunopathogenesis of these diseases may not be dependent on this state of immediate type hypersensitivity. It is concluded that the loss of balance within functional distinct macrophage populations within the lung may represent the fundamental problem in allergic lung disease. This possibility is discussed in the light of other work in this field.