BACKGROUND: Major operative injury initiates immunologic changes that may result in a systemic inflammatory response, leading to organ dysfunction/sepsis. Catecholamines seem to be key mediators. The effects of beta(2) receptor blockade in vitro and in vivo before and after operative injury were studied to clarify their role. METHODS: In vitro studies were done in RAW 264.7 cells using epinephrine (50 micromol/L) with or without alpha(2)- and beta(2)-receptor blockade. Comparative gene expression analysis on the Toll-like receptor (TLR)-4 receptor signaling pathway was performed between RAW cells pretreated with epinephrine with subsequent lipopolysaccharide (LPS) stimulation versus LPS alone. Confirmatory studies were performed by real-time reverse transcription polymerase chain reaction (RT-PCR). Tumor necrosis factor (TNF)-alpha gene and protein expression were determined via real time RT-PCR and enzyme-linked immunosorbent assay, respectively. In vivo, Balb/C mice received no treatment nor injury (group I). Group II received operative injury and vehicle injection, group III received ICI 118,551 (beta(2)-receptor antagonist) 30 minutes before or in separate studies after operative injury. At 7 days, splenic macrophages were harvested and cytokine production was measured with or without LPS. In separate experiments, cecal ligation and puncture (CLP) was done 7 days after operation and survival determined. RESULTS: In vitro studies demonstrated that epinephrine pretreatment significantly increased TNF-alpha production with LPS stimulation (P < .05). beta(2)-Receptor blockade significantly attenuated (P < .05) LPS stimulated TNF-alpha production. MD-2, an essential coactivator of TLR-4 signaling, gene expression was significantly elevated when cells were pretreated with epinephrine before LPS exposure (P < .001). In vivo studies demonstrated a significant decrease (P < .05) in TNF-alpha and interleukin-6 production in the ICI 118,551 group. Similar findings were demonstrated measuring monocyte chemoattractant protein-1 and interferon-gamma cytokine levels (P < .05) versus no treatment. ICI 118,551 treatment 30 minutes before operation demonstrated a 31% reduction in mortality after CLP (P < .05). CONCLUSION: This study demonstrates that beta(2)-receptor blockade reduces macrophage cytokine production and improves survival showing the critical importance of catecholamines to the immunologic response in surgery.
BACKGROUND: Major operative injury initiates immunologic changes that may result in a systemic inflammatory response, leading to organ dysfunction/sepsis. Catecholamines seem to be key mediators. The effects of beta(2) receptor blockade in vitro and in vivo before and after operative injury were studied to clarify their role. METHODS: In vitro studies were done in RAW 264.7 cells using epinephrine (50 micromol/L) with or without alpha(2)- and beta(2)-receptor blockade. Comparative gene expression analysis on the Toll-like receptor (TLR)-4 receptor signaling pathway was performed between RAW cells pretreated with epinephrine with subsequent lipopolysaccharide (LPS) stimulation versus LPS alone. Confirmatory studies were performed by real-time reverse transcription polymerase chain reaction (RT-PCR). Tumor necrosis factor (TNF)-alpha gene and protein expression were determined via real time RT-PCR and enzyme-linked immunosorbent assay, respectively. In vivo, Balb/C mice received no treatment nor injury (group I). Group II received operative injury and vehicle injection, group III received ICI 118,551 (beta(2)-receptor antagonist) 30 minutes before or in separate studies after operative injury. At 7 days, splenic macrophages were harvested and cytokine production was measured with or without LPS. In separate experiments, cecal ligation and puncture (CLP) was done 7 days after operation and survival determined. RESULTS: In vitro studies demonstrated that epinephrine pretreatment significantly increased TNF-alpha production with LPS stimulation (P < .05). beta(2)-Receptor blockade significantly attenuated (P < .05) LPS stimulated TNF-alpha production. MD-2, an essential coactivator of TLR-4 signaling, gene expression was significantly elevated when cells were pretreated with epinephrine before LPS exposure (P < .001). In vivo studies demonstrated a significant decrease (P < .05) in TNF-alpha and interleukin-6 production in the ICI 118,551 group. Similar findings were demonstrated measuring monocyte chemoattractant protein-1 and interferon-gamma cytokine levels (P < .05) versus no treatment. ICI 118,551 treatment 30 minutes before operation demonstrated a 31% reduction in mortality after CLP (P < .05). CONCLUSION: This study demonstrates that beta(2)-receptor blockade reduces macrophage cytokine production and improves survival showing the critical importance of catecholamines to the immunologic response in surgery.
Authors: Mohan R Dasu; Sandra R Ramirez; Thi Dinh La; Farzam Gorouhi; Chuong Nguyen; Benjamin R Lin; Chelcy Mashburn; Heather Stewart; Thomas R Peavy; Jan A Nolta; Roslyn R Isseroff Journal: Stem Cells Transl Med Date: 2014-04-23 Impact factor: 6.940
Authors: Ahmad Mohammad Ismail; Tomas Borg; Gabriel Sjolin; Arvid Pourlotfi; Sebastian Holm; Yang Cao; Per Wretenberg; Rebecka Ahl; Shahin Mohseni Journal: Trauma Surg Acute Care Open Date: 2020-07-29
Authors: Christine E Pullar; Gabrielle S Le Provost; Andrew P O'Leary; Sian E Evans; Brian S Baier; R Rivkah Isseroff Journal: J Invest Dermatol Date: 2012-04-12 Impact factor: 8.551
Authors: Min-Ho Kim; Farzam Gorouhi; Sandra Ramirez; Jennifer L Granick; Barbara A Byrne; Athena M Soulika; Scott I Simon; R Rivkah Isseroff Journal: J Invest Dermatol Date: 2013-10-11 Impact factor: 8.551
Authors: Alex P Di Battista; Shawn G Rhind; Michael G Hutchison; Syed Hassan; Maria Y Shiu; Kenji Inaba; Jane Topolovec-Vranic; Antonio Capone Neto; Sandro B Rizoli; Andrew J Baker Journal: J Neuroinflammation Date: 2016-02-16 Impact factor: 8.322