Pentoxifylline selectivity inhibits tumor necrosis factor synthesis in the arterial wall

Pentoxifylline (PTX) has been reported to potentially inhibit tumor necrosis factor (TNF) synthesis by monocytes/macrophages. Because inflammatory processes involve both leukocytes and vascular cells, we tested the effects of PTX on TNF and interleukin-6 (IL-6) production by the vessel wall in response to lipopolysaccharide (LPS). Rings of rat thoracic aorta were incubated for 24 h in DMEM containing antibiotics and 1% fetal calf serum in the presence of 1 microgram/ml LPS. TNF and IL-6 were biologically assayed using L-M fibroblast cytotoxicity and B9 hybridoma cell proliferation, respectively. Maximal LPS-induced production of TNF and IL-6 by the aorta was 0.77 +/- 0.04 and 23.3 +/- 3.5 x 10(3) U/mg dry weight, respectively. The addition of PTX dose-dependently suppressed the production of TNF by 26 +/- 7%, 58 +/- 6%, and 85 +/- 9% at 10, 100, and 1,000 microM, respectively. This effect was selective for TNF, because the production of IL-6 was not affected by any dose of PTX, suggesting a selective gene regulation of TNF and IL-6 in vascular cells. These results may have clinical implications. PTX may be useful in vascular inflammatory diseases, in which serum TNF levels have been shown to be correlated with the severity of the disease.