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Anesthetics impact the resolution of inflammation.

Chiang N, Schwab JM, Fredman G, Kasuga K, Gelman S, Serhan CN - PLoS ONE (2008)

Bottom Line: Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages.Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1.In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1).

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Local and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine) and a widely used inhaled anesthetic (isoflurane) impact the active process of resolution of inflammation.

Methods and findings: Using murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages. Addition of a lipoxin A(4) stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri) approximately 50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1). The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation, namely lidocaine delayed the onset of resolution (T(max)), while isoflurane shortened resolution interval (Ri).

Conclusions: Taken together, both local and volatile anesthetics impact endogenous resolution program(s), altering specific resolution indices and selective cellular/molecular components in inflammation-resolution. Isoflurane enhances whereas lidocaine impairs timely resolution of acute inflammation.

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Related in: MedlinePlus

Lidocaine did not directly alter selective eicosanoid levels in cell-free exudates: LXA4 rescues lidocaine-delayed resolution.(A) Cell-free lavages from murine peritoneum were collected at indicated time points after zymosan challenge (1 mg/ml). LXA4, LTB4 and PGE2 amounts were determined by ELISA. Results are expressed as the mean±SEM from duplicates of n = 3, and were expressed as amounts (ng/ml). (B) Mice were injected with zymosan A together with lidocaine (0.08%), ATLa (300 ng), or lidocaine plus ATLa. Peritoneal lavages were collected at 24 h, and total leukocytes enumerated. Results are expressed as mean±SEM from n = 3. *p = 0.03 **p = 0.01 when compared to mice treated with zymosan A alone. ***p = 0.04 when compared to mice treated with zymosan A and lidocaine.
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pone-0001879-g002: Lidocaine did not directly alter selective eicosanoid levels in cell-free exudates: LXA4 rescues lidocaine-delayed resolution.(A) Cell-free lavages from murine peritoneum were collected at indicated time points after zymosan challenge (1 mg/ml). LXA4, LTB4 and PGE2 amounts were determined by ELISA. Results are expressed as the mean±SEM from duplicates of n = 3, and were expressed as amounts (ng/ml). (B) Mice were injected with zymosan A together with lidocaine (0.08%), ATLa (300 ng), or lidocaine plus ATLa. Peritoneal lavages were collected at 24 h, and total leukocytes enumerated. Results are expressed as mean±SEM from n = 3. *p = 0.03 **p = 0.01 when compared to mice treated with zymosan A alone. ***p = 0.04 when compared to mice treated with zymosan A and lidocaine.

Mentions: Specialized lipid mediators play a key role in resolution of inflammation [5] with some specifically switched on during the resolution phase to promote resolution [17]. Here, key lipid mediators were monitored in murine exudates, including lipoxin (LX) A4, an anti-inflammatory and pro-resolution mediator, and the pro-inflammatory LTB4 and prostaglandin (PG) E2. In this system, the maximal levels present in cell-free lavages of the exudates of both LTB4 and LXA4 were obtained at 4 h. These subsequently subsided within 24 h (Fig. 2A). Lidocaine did not significantly alter the levels of LXA4, LTB4 or PGE2 present in these cell-free lavages of the peritoneal exudates. Thus, these eicosanoids likely reflect the profile from resident peritoneal cells including macrophages as are less likely to report eicosanoids generated by the infiltrating leukocytes.


Anesthetics impact the resolution of inflammation.

Chiang N, Schwab JM, Fredman G, Kasuga K, Gelman S, Serhan CN - PLoS ONE (2008)

Lidocaine did not directly alter selective eicosanoid levels in cell-free exudates: LXA4 rescues lidocaine-delayed resolution.(A) Cell-free lavages from murine peritoneum were collected at indicated time points after zymosan challenge (1 mg/ml). LXA4, LTB4 and PGE2 amounts were determined by ELISA. Results are expressed as the mean±SEM from duplicates of n = 3, and were expressed as amounts (ng/ml). (B) Mice were injected with zymosan A together with lidocaine (0.08%), ATLa (300 ng), or lidocaine plus ATLa. Peritoneal lavages were collected at 24 h, and total leukocytes enumerated. Results are expressed as mean±SEM from n = 3. *p = 0.03 **p = 0.01 when compared to mice treated with zymosan A alone. ***p = 0.04 when compared to mice treated with zymosan A and lidocaine.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2268966&req=5

pone-0001879-g002: Lidocaine did not directly alter selective eicosanoid levels in cell-free exudates: LXA4 rescues lidocaine-delayed resolution.(A) Cell-free lavages from murine peritoneum were collected at indicated time points after zymosan challenge (1 mg/ml). LXA4, LTB4 and PGE2 amounts were determined by ELISA. Results are expressed as the mean±SEM from duplicates of n = 3, and were expressed as amounts (ng/ml). (B) Mice were injected with zymosan A together with lidocaine (0.08%), ATLa (300 ng), or lidocaine plus ATLa. Peritoneal lavages were collected at 24 h, and total leukocytes enumerated. Results are expressed as mean±SEM from n = 3. *p = 0.03 **p = 0.01 when compared to mice treated with zymosan A alone. ***p = 0.04 when compared to mice treated with zymosan A and lidocaine.
Mentions: Specialized lipid mediators play a key role in resolution of inflammation [5] with some specifically switched on during the resolution phase to promote resolution [17]. Here, key lipid mediators were monitored in murine exudates, including lipoxin (LX) A4, an anti-inflammatory and pro-resolution mediator, and the pro-inflammatory LTB4 and prostaglandin (PG) E2. In this system, the maximal levels present in cell-free lavages of the exudates of both LTB4 and LXA4 were obtained at 4 h. These subsequently subsided within 24 h (Fig. 2A). Lidocaine did not significantly alter the levels of LXA4, LTB4 or PGE2 present in these cell-free lavages of the peritoneal exudates. Thus, these eicosanoids likely reflect the profile from resident peritoneal cells including macrophages as are less likely to report eicosanoids generated by the infiltrating leukocytes.

Bottom Line: Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages.Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1.In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1).

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT

Background: Local and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine) and a widely used inhaled anesthetic (isoflurane) impact the active process of resolution of inflammation.

Methods and findings: Using murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages. Addition of a lipoxin A(4) stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri) approximately 50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1). The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation, namely lidocaine delayed the onset of resolution (T(max)), while isoflurane shortened resolution interval (Ri).

Conclusions: Taken together, both local and volatile anesthetics impact endogenous resolution program(s), altering specific resolution indices and selective cellular/molecular components in inflammation-resolution. Isoflurane enhances whereas lidocaine impairs timely resolution of acute inflammation.

Show MeSH
Related in: MedlinePlus