Lidocaine suppresses mouse Peyer's Patch T cell functions and induces bacterial translocation

Kawasaki, Takashi; Kawasaki, Chika; Sata, Takeyoshi; Chaudry, Irshad H.

doi:10.1016/j.surg.2010.03.024

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…It is difficult to translate those in vitro results to a clinical immunosuppressive effect of lidocaine because Jurkat cells are derived from the peripheral blood of a patient with T cell leukemia and express the uncontrolled characteristics of cancer cells ( 89 ). More physiologically, lidocaine also had an immunosuppressive effect on isolated mouse T cells derived from Peyer’s patches ( 90 ) and reduced the secretion of pro-inflammatory cytokines in freshly isolated peripheral blood T cells ( 88 ). In addition, lidocaine inhibited the differentiation of Th1 cell responses of mice dendritic cells ( 91 ).…”

Section: Effects On the Immune System: Implication For Malignant Disementioning

confidence: 99%

The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

Chamaraux-Tran

Piegeler

2017

Front. Med.

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Surgical removal of the primary tumor in solid cancer is an essential component of the treatment. However, the perioperative period can paradoxically lead to an increased risk of cancer recurrence. A bimodal dynamics for early-stage breast cancer recurrence suggests a tumor dormancy-based model with a mastectomy-driven acceleration of the metastatic process and a crucial role of the immunosuppressive state during the perioperative period. Recent evidence suggests that anesthesia could also influence the progress of the disease. Local anesthetics (LAs) have long been used for their properties to block nociceptive input. They also exert anti-inflammatory capacities by modulating the liberation or signal propagation of inflammatory mediators. Interestingly, LAs can reduce viability and proliferation of many cancer cells in vitro as well. Additionally, retrospective clinical trials have suggested that regional anesthesia for cancer surgery (either with or without general anesthesia) might reduce the risk of recurrence. Lidocaine, a LA, which can be administered intravenously, is widely used in clinical practice for multimodal analgesia. It is associated with a morphine-sparing effect, reduced pain scores, and in major surgery probably also with a reduced incidence of postoperative ileus and length of hospital stay. Systemic delivery might therefore be efficient to target residual disease or reach cells able to form micrometastasis. Moreover, an in vitro study has shown that lidocaine could enhance the activity of natural killer (NK) cells. Due to their ability to recognize and kill tumor cells without the requirement of prior antigen exposure, NKs are the main actor of the innate immune system. However, several perioperative factors can reduce NK activity, such as stress, pain, opioids, or general anesthetics. Intravenous lidocaine as part of the perioperative anesthesia regimen would be of major interest for clinicians, as it might bear the potential to reduce the risk of cancer recurrence or progression patients undergoing cancer surgery. As a well-known pharmaceutical agent, lidocaine might therefore be a promising candidate for oncological drug repurposing. We urgently need clinical randomized trials assessing the protective effect of lidocaine on NKs function and against recurrence after cancer surgery to achieve a “proof of concept.”

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Section: Effects On the Immune System: Implication For Malignant Disementioning

confidence: 99%

The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

Chamaraux-Tran

Piegeler

2017

Front. Med.

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“…In addition, the results of the present study revealed that intraoperative systemic lidocaine attenuated the apoptosis of PBL cells induced by surgical stressors. However, previous in vitro studies have demonstrated the opposite conclusions regarding cell proliferation (17,18) and apoptosis (19,20). This indicates that the protective effects of lidocaine on CMI in vivo are not directly due to its effects on lymphocytes, and the underlying mechanisms require further exploration.…”

Section: Discussionmentioning

confidence: 93%

Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy

Wang

Yan

Liu

et al. 2015

Molecular Medicine Reports

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Abstract. Surgical procedures cause a decrease in lymphocyte proliferation rate, an increase in apoptosis and shifts the balance of T-helper (Th)1/Th2 cells towards anti-cell-mediated immunity (CMI) Th2 dominance, which is relevant to the immunosuppressive effects of CMI, postoperative septic complications and the formation of tumor metastasis. Previous studies have revealed that lidocaine exhibits antibacterial actions; regulating inflammatory responses, reducing postoperative pain and affecting the duration spent in hospital. Thus, the present study hypothesized that lidocaine may exert a protective effect on the CMI of patients undergoing surgery for the removal of a primary tumor. A total of 30 adult female patients diagnosed with cervical cancer were recruited to the present study and were randomized into two groups. The lidocaine group received an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by continuous infusion at 1.5 mg/kg/h until discharge from the operating room. The control group received the same volume of normal saline. A 10 ml sample of venous blood was drawn, and the lymphocytes were isolated using Ficoll-paque 1 day prior to surgery, at discharge from the operating room and 48 h post-surgery. The proliferation rate of the lymphocytes was assessed using a Cell Counting Kit-8 assay and was found to be higher in the lidocaine group. The early apoptosis of lymphocytes was attenuated following lidocaine treatment at 48 h post-surgery, as detected using flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide staining. The level of interferon (IFN)-γ in the serum at 48 h was significantly decreased following surgery in the control group, compared with the pre-surgical values (3.782±0.282, vs. 4.089±0.339 pg/ml, respectively) and the ratio of IFN-γ to interleukin-4 was well preserved in the lidocaine group. In conclusion, the present study demonstrated that the intraoperative systemic administration of lidocaine exerted a protective effect on CMI in patients with cervical cancer undergoing radical hysterectomy. This may be beneficial in reducing the occurrence of postoperative septic complications and tumor metastasis formation.

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“…10,12,13,70,84,191 Lidocaine has been shown to inhibit cell proliferation, cytokine production, and mitogen-activated protein kinase activation in T cells and upregulate regulatory T-cells that promote an antiinflammatory t-cell phenotype. 84,94,101,118 One study in mouse showed that release of antiinflammatory cytokine IL10 may be enhanced by lidocaine. 211 Questions remain as to how long the immunomodulatory effects of LAs persist after drug administration is complete.…”

Section: Local Anestheticsmentioning

confidence: 99%

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

DeMarco

Nunamaker

2019

comp med

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One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to balance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particular immune function or model are incomplete or don't exist. Further complicating the picture is evidence of the very tight integration and bidirectional functionality between the immune system and branches of the nervous system involved in nociception and pain. These relationships have advanced the concept of understanding pain as a protective neuroimmune function and recognizing pathologic pain as a neuroimmune disease. This review strives to summarize extant literature on the effects of pain and analgesia on immune system function and inflammation in the context of preclinical in vivo studies. The authors hope this work will help to guide selection of analgesics for preclinical studies of inflammatory disease and immune system function.

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Lidocaine suppresses mouse Peyer's Patch T cell functions and induces bacterial translocation

Cited by 9 publications

References 44 publications

The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy

A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies

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