Effects of cytokines and minocycline on subacute lung injuries induced by repeated injection of lipopolysaccharide.

Pathological changes were seen in the lungs of ddY mice one week after repeated intraperitoneal injections of lipopolysaccharide (LPS) of Klebsiella pneumoniae. The infiltration of polymorphonuclear cells (PMN), mainly neutrophils, and lymphocytes into the alveolar septum, the infiltration of PMN into perivascular areas and microthrombi were recognized in this murine model. The blood levels of TNF alpha and IL-1 alpha did not rise at this time, suggesting that the most important cytokine promoting inflammation one week after LPS stimulation was neither TNF alpha nor IL-1 alpha. In the lungs of mice administered minocycline together with LPS, lymphocyte infiltration of alveoli and perivascular areas as well as microthrombi were suppressed. The blood levels of TNF alpha, IL-1 alpha, IL-4 and IL-6 were elevated in these groups, suggesting the suppression of pathological changes to be associated with the anti-inflammatory effect of IL-6 and/or persistent elevation of TNF alpha and/or IL-1 alpha levels. In conclusion, subacute pathological changes in the lung were induced by repeated intraperitoneal injections of LPS to mice. These pathological changes were suppressed by minocycline, suggesting the anti-inflammatory effects of this antibiotic to be the result of stimulating certain cytokines.