Selective differences in macrophage populations and monokine production in resolving pulmonary granuloma and fibrosis

Abstract

Alveolar macrophages (AM) and their production of interleukin-1-like activity (IL-1) and macrophage-derived growth factor for fibroblasts (MDGF) were examined during chronic inflammatory reactions leading to either granuloma formation or fibrosis. Groups of five rats each received, respectively, a single transtracheal injection of xonotlite, attapulgite, short chrysotile 4T30, UICC chrysotile B asbestos, or saline. One month later, such treatments induced either no change (xonotlite), granuloma formation (attapulgite and short chrysotile 4T30), or fibrosis (UICC chrysotile B). By 8 months, however, the granulomatous reactions had resolved or greatly diminished, whereas the fibrosis persisted irreversibly. Parallel examination of cell populations obtained by bronchoalveolar lavage revealed that multinucleated giant macrophages (MGC) were present in lavage fluids of animals with resolving granulomatous reactions but absent in those obtained from animals with lung fibrosis. Evaluation of monokine production by inflammatory macrophages also revealed significant differences. Enhanced production of IL-1-like activity was seen in both types of lung injury, although especially during the early stage (1 month) and decreased thereafter (8 months). By contrast, augmentation of MDGF production was observed in animals with lung fibrosis only and persisted up to 9 months. Taken together, these data indicate that production of selected cytokines, as well as AM differentiation along a given pathway, may modulate the outcome of a chronic inflammatory response.