Propranolol restores the tumor necrosis factor-alpha response of circulating inflammatory monocytes and granulocytes after burn injury and sepsis.
Propranolol restores the tumor necrosis factor-alpha response of circulating inflammatory monocytes and granulocytes after burn injury and sepsis.
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DOI：
10.1097/bcr.0b013e3181921f22
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Shankar R
中科院分区：
文献类型：
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作者：
Muthu K;He LK;Szilagyi A;Stevenson J;Gamelli RL;Shankar R
Beta-adrenergic blockade ameliorates the hypermetabolism and catabolism in severe burn injury. Despite the salutary effects of beta-adrenergic blockade, the immunological responses that accompany beta blockade are not known. We have shown that burn sepsis is associated with increased sympathetic activation leading to altered monocytopoiesis and cytokine release in MØ. Recent evidence suggests that murine MØ expressing F4/80+Gr1+ are the inflammatory phenotype. Here we report that propranolol given after burn sepsis modulates the number and function of myeloid cells in circulation. B6D2F1 male mice were divided into sham (S), burn (B) and burn sepsis (BS) groups. Dorsal hair was shaved from S, B & BS; B & BS received 15% scald burn; BS was inoculated with Pseudomonas aeruginosa (PA 14, 4–5K CFU) at the burn site. Mice from each group were then subjected to two different treatment regimens. One set received subcutaneous injections of propranolol (5mg/Kg body wt.) at 24h and 48h after the injury while the control groups received saline. Blood was collected by cardiac puncture at 72h. The distribution of total F4/80+ monocyte population was determined by flow cytometry. Inflammatory monocyte subset was gated on Gr-1+ expression in the F4/80+ fraction. LPS stimulated intracellular TNF-α (ic-TNF) was also measured as an indicator of inflammatory response. The total F4/80+ monocyte fraction was significantly increased in BS (45±0.8%) vs. S and B (10±0.8%; 9.5±0.6%). Propranolol treatment for 2 days reduced the number of circulating monocytes by 60% in BS. The mean fluorescent intensity (MFI) of ic-TNF produced per cell (F4/80+Gr1+ MØ) was significantly decreased in B and BS (S: 3043±213, B: 1638±343, BS: 1463±67). Of importance, propranolol treatment partially restored the MFI of ic-TNF (2177±114) and increased the percentage of inflammatory monocyte subset (F4/80+Gr1+) in BS by 70% compared to saline treatment. In contrast, beta-blockade after BS increased the percentage of granulocytes in circulation (28.4±3.6% in BS propranolol vs. 15.4±0.3% in BS Saline; p<0.05) and augmented their TNF production (MFI = 903±102 in BS propranolol vs. 644±5 in BS Saline; p<0.05). Propranolol reverses burn sepsis-induced monocytosis and simultaneously increases the number of granulocytes and enhances the inflammatory potential of the granulocytes and inflammatory monocyte subsets in circulation suggesting that monitoring MØ subsets and granulocytes in blood is a reliable biomarker to predict the efficacy of beta blockade.
