The role of monokines in granuloma formation in mice: the ability of interleukin 1 and tumor necrosis factor-alpha to induce lung granulomas.

Granulomatous inflammation is associated with many significant human diseases, including tuberculosis, leprosy, sarcoidosis, parasite infection, and berylliosis. Very little is known about the basic mechanism of this type of inflammation. In the present study, we showed that pulmonary granulomas were induced in mice by the intratracheal injection of agarose beads coupled to recombinant interleukin 1 (IL-1) or tumor necrosis factor-alpha (TNF-alpha). Histologically, the bulk of granulomas was composed of macrophages and their derivatives. In contrast, the inflammatory reactions induced by beads coupled to either recombinant IL-2 or murine interferon-gamma were considerably smaller than those induced by beads coupled to monokines. These results suggest that macrophages and monokines such as IL-1 and TNF-alpha, but not T cell-derived lymphokines, play an essential role in granuloma formation.