Introduction: Propranolol (?-blocker) decreases the incidence of sepsis and improves mortality of critically ill patients. The aim of the present study is to determine the effects of propranolol on cell survival, cell activity, apoptosis and pro-inflammatory response in a human macrophage like cell line (THP-1 cells) stressed with lipopolysaccharide (LPS).

Background: We showed before that high dose of LPS treatment induces apoptosis in differentiated THP-1 cells. In addition, propranolol attenuates the systemic inflammatory response in endotoxemic as well as in thermally injured rats by decreasing the pro-inflammatory and increasing the anti-inflammatory cytokines. However, there is little knowledge about the effect of propranolol on macrophages.

Methods: Differentiated THP-1 cells were stressed with LPS in the presence of (or without) propranolol. Cell viability was analyzed by MTT assay and Trypan blue staining, and Caspase-3 activity was measured by the fluorescence of Z-DEVD-R110. JC-1 assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining was also used to confirm apoptosis. Tumor necrosis factor (TNF) and interleukin-1? (IL1-?) were measured to determine the effect of propranolol on pro-inflammatory cytokine expression.

Results: MTT assay and Trypan blue exclusion suggest that propranolol increases cell viability in LPS-treated THP-1 cells. Because caspase-3 plays a major role in apoptotic signaling, we measured the enzyme activity of caspase-3 by fluorescent substrate. We confirmed that the addition of propranolol suppressed caspase-3 activation induced by high dose of LPS to almost control level in a dose dependent manner (range: 10-100?M; Figure). Propranolol also significantly decreased TNF and IL1-? in differentiated THP-1 cells.

Conclusion: Our results indicate that propranolol exerts anti-apoptotic effects in differentiated THP-1 cells, and it may reduce the expression of pro-inflammatory cytokines and apoptosis in endotoxemic human macrophages. Thus, application of propranolol to patients suffering sepsis after traumatic injuries may be beneficial by improving survival of macrophages meanwhile calming down inflammatory responses.