Lidocaine regulates the expression of cytokines and NF-κB signaling pathway in a dose-dependent manner.

<p>(A) Bone marrow-derived dendritic cells were stimulated with 100 ng/ml of LPS together with increasing concentrations of lidocaine for 4 h. The mRNA levels of the indicated genes were analyzed by quantitative RT-PCR. (B) Raw 264.7 cells were treated with increasing doses of lidocaine for 2 h and stimulated with LPS for 20 min. The expression of IκB-α was examined by western blot. All experiments were performed at least three times. Data shown are mean ± SEM. *<i>p</i><0.05; **<i>p</i><0.01.</p

Effects of lidocaine on the expression of various cytokines upon LPS stimulation.

<p>Bone marrow-derived dendritic cells were stimulated with 100 ng/ml of LPS in the presence of vehicle (EtOH) or 0.2 mg/ml lidocaine for 4 h and 24 h to examine mRNA expression and cytokine production, respectively. (A) The mRNA levels of the indicated genes were analyzed by quantitative RT-PCR. (B) The amounts of each cytokine produced were measured by ELISA. All experiments were performed at least three times. Data shown are mean ± SEM. *<i>p</i><0.05; ***<i>p</i><0.001; ND, not detected.</p

Lidocaine inhibits dendritic cell-mediated Th1 cell differentiation <i>in vitro</i>.

<p>Naïve CD4⁺ T cells were either co-cultured with bone marrow-derived dendritic cells in the presence of soluble anti-CD3 and LPS, or in anti-CD3, CD28 pre-coated plates in the presence of IL–2 and IL–12 for Th1 cell differentiation. Lidocaine was added at a concentration of 0.2 mg/ml. (A & B) The frequencies of IFNγ or IL–17 producing cells among CD4⁺ T cells. (C) The mRNA levels of the indicated genes. (D) The levels of IFN-γ in the cultured supernatants of naïve CD4⁺ T cells cultured with vehicle- or lidocaine-conditioned media. Data represent at least three independent experiments. Data shown are mean ± SEM. **<i>p</i><0.01; ***<i>p</i><0.001; NS, not significant.</p

Regulation of cytokines expression in dendritic cells in response to various TLR ligands by lidocaine.

<p>(A & B) Bone marrow-derived dendritic cells were stimulated with LPS (100 ng/ml), poly(I:C) (1 μg/ml) or R837 (1 μg/ml) in the presence of lidocaine (0.4 mg/ml) or vehicle. The amounts of IL–6 and TNF-α in the supernatant were measured by ELISA. (C) The mRNA levels of the indicated genes were analyzed by quantitative RT-PCR. Data represent at least two independent experiments. Data shown are mean ± SEM. *<i>p</i><0.05; **<i>p</i><0.01; ND, not detected.</p

Lidocaine inhibits dendritic cell-mediated Th1 cell differentiation while having little effects on dendritic cell-mediated Th2, Th17, regulatory T cell differentiation <i>in vitro</i>.

<p>Naïve CD4⁺ T cells were co-cultured with bone marrow-derived dendritic cells with Th1, Th17, Th2 or regulatory T cell differentiation conditioned-media or cultured with plate-coated anti-CD3 and anti-CD28 with supernatant of dendritic cells stimulated with LPS in the presence of lidocaine (0.2 mg/ml or indicated dose) or vehicle. (A-D) The frequencies of IFN-γ, IL–17, IL–4/5 or Foxp3 positive cells among CD4⁺ population were measured by flow cytometer. (E) The level of IFN-γ was measured using co-cultured supernatants from Th1 differentiation condition. Data represent at least two independent experiments. Data shown are mean ± SEM. *<i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001; NS, not significant.</p

Inhibition of dendritic cell-mediated antigen-specific Th1 cell responses by lidocaine <i>in vivo</i>.

<p>Bone marrow-derived dendritic cells were pulsed with OVA_323-339 in the presence of lidocaine or vehicle before being transferred into OT-II TcR transgenic mice (n = 3~4). (A and B) The frequencies of IFN- γ producers among Vα2⁺ cells. (C) The amounts of the indicated cytokines in the supernatant of splenocyte stimulated with OVA_323-339 were measured by ELISA. Data represent two independent experiments. Data shown are mean ± SEM. *<i>p</i><0.05.</p

Effects of palonosetron for prophylaxis of postoperative nausea and vomiting in high-risk patients undergoing total knee arthroplasty: A prospective, randomized, double-blind, placebo-controlled study

<div><p>Background</p><p>The preemptive multimodal pain protocols used in total knee arthroplasty (TKA) often cause emesis postoperatively. We investigated whether palonosetron prophylaxis reduces postoperative nausea and vomiting (PONV) in high-risk patients after TKA.</p><p>Methods</p><p>We randomized 120 female patients undergoing TKA to receive either palonosetron (0.075 mg, intravenous) or no antiemetic prophylaxis (0.9% saline, control group). All patients were given spinal anesthesia, a continuous femoral nerve block, and fentanyl-based intravenous patient controlled analgesia. Patients undergoing staged bilateral TKA were assigned to one group for the first knee and the other group for the second knee. The overall incidence of PONV, the incidences of both nausea and vomiting, severity of nausea, complete response, requirement for rescue antiemetics, pain level, opioid consumption, and satisfaction scores were evaluated during three periods: 0–2, 2–24, and 24–48 h postoperatively. We also compared PONV and pain between the first and second TKA.</p><p>Results</p><p>The incidence of PONV during the first 48 h was lower in the palonosetron group compared with the controls (22 <i>vs</i>. 41%, <i>p</i> = 0.028), especially 2–24 h after surgery, as was the nausea and vomiting respectively. The severity of nausea was lower in the palonosetron group (<i>p</i> = 0.010). The complete response rate (93 <i>vs</i>. 73%, <i>p</i> = 0.016) and satisfaction score (84 ± 12 <i>vs</i>. 79 ± 15, <i>p</i> = 0.032) were higher in the palonosetron group during 2–24 h after surgery. Patients who underwent a second operation complained of more severe pain, and consumed more opioids than those of the first operation. There was no difference in the incidence of PONV between the first and second operations.</p><p>Conclusions</p><p>Palonosetron prophylaxis reduced the incidence and severity of PONV in high-risk patients managed with multimodal pain protocol for 48 h, notably 2–24 h after TKA.</p></div

Complete response rates, requirement of rescue antiemetics, and satisfaction score after surgery.

<p>Complete response rates, requirement of rescue antiemetics, and satisfaction score after surgery.</p

CONSORT flow diagram.

<p>FNB, femoral nerve block.</p

Patients, operative and anesthetic characteristics.

<p>Patients, operative and anesthetic characteristics.</p