Abstract
Granulomas are focal, predominantly mononuclear tissue inflammations evoked by persistent irritants. The lesions are classified as hypersensitivity and foreign-body granulomas. In view of the predominant participation of macrophages in granulomas such as hypersensitivity, foreign-body and tuberculous lesions, it is reasonable that macrophages and their products may be involved in granulomatous inflammation. We developed experimental murine models of hypersenstivity, foreigin-body and BCG granulomas. Presence of macrophage-derived cytokines (monokines) such as interleukin 1 (IL-1) is a common feature in granulomatous lesions. IL-1 activity is well associated with size/activity of lesions. Also, our studies have demonstrated that macrophages and monokines such as IL-1 and tumor necrosis factor-α (TNF-α) play a critical role in the development of granulomas in vivo and in vitro. To investigate modulatory mechanisms of granuloma formation, we examined the effects of various mediators such as IL-1, TNF-α, interferon-γ (IFN-γ), IL-4, IL-6, transforming growth factor-β (TGF-β), dexamethasone and prostaglandin E2 (PGE2) on the development of lesions. The lesions were suppressed by dexametheasone, PGE2 or certain T cellderived lymphokines such a IL-4 and IFN-γ. These results suggest that suppressive signals are different from granulomatogenic cytokines including IL-1 and TNF-α and that granulomas are regulated by multiactor dependent mechanisms.
