Pentoxifylline reduces indirect lung injury of fresh water drowning in canis

BACKGROUND: Previous studies have suggested that pentoxifylline (PTX) exerts multiple beneficial effects on the inflammatory cascade, particularly on the function of neutrophils. We investigated whether continuous infusion of PTX could reduce indirect lung injury (ILI) caused by fresh water drowning and if so, what is the possible molecular mechanism. METHODS: Twenty 4 male canis were divided randomly into control group, fresh water drowning group (right lung), drowning treated with PTX group and PTX alone group. At different time points after drowning, the changes of hemodynamic parameters and wet/dry weight of indirect lung (left lung) tissues were compared among these 4 groups. Other measures included lung histopathology, PMN infiltration assessed by immune staining, CD11b, ICAM-1 mRNA and TNF-alphamRNA in left lung detected by RT-PCR. NF-kappaB activation in blood neutrophils and lungs were measured with electrophoretic mobility shift assay (EMSA). RESULTS: Animals treated with PTX showed a significant reduction in lung injury. PTX suppressed drowning-induced ICAM-1 and TNF-alphamRNA elevation and inhibited NF-kappaB activation in blood neutrophils and lungs. CONCLUSIONS: Continuous infusion of PTX reduces ILI caused by fresh water drowning. PTX decreases expression of ICAM-1 and TNF-alpha, possibly via inhibition of NF-kappaB.