Intratracheal instillation of AMD in vivo or exposure of alveolar macrophages to AMD in vitro led to TNF production (Futamura, 1996; Reinhart and Gairola, 1997) . AMD treatment also increased TNF production by alveolar macrophages on LPS stimulation (Punithavathi et al., 2003) . In the present study, treatment of rats with AMD alone did not cause serum TNF elevation, but it did increase the concentration of TNF in serum of LPS-treated rats. These results suggest that the increased appearance of TNF in AMD/LPS-cotreated rats was probably not an additive effect; rather, AMD appeared to potentiate the production or diminish the clearance of TNF caused by LPS. The concentration of TNF in serum increases rapidly in LPS-treated rats, peaks at around 1.5-2 h, and then returns to basal levels at around 6 h (Tukov et al., 2007) . In the present study, the concentration of TNF around the peak time (i.e., 2 h) in LPS-cotreated rats was not affected by AMD, but the TNF concentration was greater in AMD-cotreated rats at a later time (4 h). These data suggest that AMD prolonged the elevation in TNF caused by LPS administration. This seemingly small difference in TNF concentration was shown to be critical to liver pathogenesis in another drug/LPS model of liver injury involving trovafloxacin (Shaw et al., 2009b) . Accordingly, it is possible that prolongation of the LPS-induced TNF response is a critical event across models of LPS-drug interaction.