Cytokines seem to act predominantly in a paracrine manner when producing their deleterious effects during sepsis. Therefore, local TNF alpha release by pulmonary macrophages would have a central role in the pathogenesis of the adult respiratory distress syndrome (ARDS). By contrast, pentoxiphylline (PTXF) can reduce lung damage in septic animal models, and somatostatin (SS-14) has been shown to down-regulate TNF alpha-receptor expression in monocytes, suggesting an immunomodulatory action for this hormone. The aim of this work was to study the effect of PTXF and SS-14 on lipopolysaccharide (LPS)-induced TNF alpha release by human pulmonary macrophages. Macrophages were obtained from multiple organ donor lungs. Donors with either a recent history of tobacco smoking, more than 72 hr of mechanical ventilation, or any radiological pulmonary infiltrate were not included in this study. After 1 hr of culture, LPS stimulated TNF alpha release in a dose-dependent manner (2.34 +/- 0.20 and 11.32 +/- 1.38 pg/microgram protein, P < 0.01, in response to 2.5 and 10 micrograms/ml LPS, respectively). This response was significantly inhibited by both PTXF, 100 micrograms/ml (0.24 +/- 0.07 vs. 2.43 +/- 0.20, P < 0.01, and 1.30 +/- 0.08 vs. 11.32 +/- 1.38, P < 0.01, pg/micrograms protein, 2.5 and 10 micrograms/ml LPS, respectively) and SS-14, 0.4 ng/ml (0.26 +/- 0.07 vs. 2.43 +/- 0.20, P < 0.01, and 0.60 +/- 0.19 vs. 11.32 +/- 1.38, P < 0.01, pg/micrograms protein, 2.5 and 10 micrograms/ml LPS, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)