Interstitial and hemorrhagic pneumonitis induced by mycobacterial trehalose dimycolate

Intraperitoneal injection of cord factor (trehalose dimycolate, TDM) provides a model for interstitial and hemorrhagic lung disease that is produced by a chemically defined substance. A single injection of 10 μg of TDM, in light mineral oil or hexadecane, into C57BL/6 mice produces interstitial and hemorrhagic pneumonitis. Following the injection of TDM the pulmonary lesions increase gradually and become maximal by the seventh to ninth day, at which time 70% of the mice show both gross hemorrhages and dense mononuclear infiltrates; an additional 20% of the mice show only microscopic lesions. From day 14 onward the incidence and severity of the lesions decrease, and by day 28 the lungs are normal by both gross and light-microscopic examination. Only 5% of the mice succumb. Except for peritonitis other organs are not affected. Doses of 3.3 and 10 μg of TDM are equally effective in producing the lesions, but a dose of 1.0 μg of TDM causes only mild interstitial inflammation and lesser doses do not induce lesions. A single subcutaneous injection of 10 μg of TDM causes lesions in only 20% of mice. Vehicle-injected mice do not develop lesions. Electron microscopy revealed that the majority of the infiltrating cells are monocytes and macrophages and that extensive interstitial damage is produced. The mechanism of the effects of TDM is unknown and is currently under study. Our preliminary data suggest that the phenomenon is dependent upon T-lymphocytes.