Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB<sub>4</sub> release and IL‐1 secretion <i>in vitro</i>

Sinclair, Robert C.; Eriksson, Anders; Gretzer, Christina; Cassuto, Jean; Thomsen, Peter

doi:10.1111/j.1399-6576.1993.tb03693.x

Cited by 133 publications

(79 citation statements)

References 41 publications

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“…It attenuates the formation of reactive oxygen metabolites [133], and the release of leukotrienes, IL-1α [134], and histamine [135]. Similar effects have been demonstrated with bupivacaine and ropivacaine [130,131,136,137].…”

Section: Local Anestheticssupporting

confidence: 50%

Anesthesia, cytokines and cancer recurrence

Kitamura¹,

Biaso²,

Ingelmo

et al. 2015

Glob Anesth Perioper Med

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Cytokines are essential mediators for the regulation of both innate and acquired immunity and hematopoiesis. They modulate immune cell signaling, activation, adhesion and functioning. They regulate the individual response to several insults such as infection, inflammation, trauma, and pain. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines is critical for the evolution of surgical complications and tumor progression.Several drugs, including anesthetic agents, influence cytokines secretion. Opioids, inhalational agents, intravenous and local anesthetics have shown different effects on immune system and cytokine expression. Therefore, anesthesia may play an important role in postoperative recovery and outcome of cancer patients.The aim of the present article is to review the main role of some important cytokines and the effect of anesthesia techniques and drugs on their secretion. Furthermore, current clinical evidence regarding the effects of anesthesia on cancer recurrence will be discussed. Cytokines and immune systemCytokines are proteins expressed in both innate and acquired immune system and are often named according to the secreting cells (i.e., lymphocytes, interleukins, etc.). They are essential mediators of the natural (non-specific, innate) immunity, which is the initial step of the inflammatory response. They also play a pivotal role during the specific immunity, which occurs after exposure to antigens, as they regulate lymphocyte and leukocyte activation, growth and differentiation, and the immune-mediated inflammation [1].The cytokines have different structures, but also common aspects, which are summarized in Table 1.The aim of the present article is to review the main role of some important cytokines and the effect of anesthesia techniques and drugs on their secretion. Cytokines receptorsThe cytokines receptors are formed by one or more transmembrane proteins: the extracellular portion binds the cytokine, whereas the cytoplasmic part starts the signal cascade. Based on the extracellular portion, they are divided in five categories. 1) Type I receptors, which have four α-helical stands and contain four cysteine residues and the amino acid motif tryptophanserine-X-tryptophan-serine (WSXWS).2) Type II receptors, structurally similar to Type I receptors, but without the sequence WSXWS. Cytokines functionProvided that the same cytokine may be produced during both innate and acquired immunity response, cytokines can be classified according to their functions: 1)Cytokines regulating the innate immunity and secreted by stimulated macrophages; 2)Cytokines regulating the acquired immunity and secreted by lymphocytes; 3)Cytokines stimulating the hematopoiesiss and secreted by bone marrow, leucocytes and other cells. Common aspects of CytokineTheir secretion is brief and limited in time Cytokine expressed during the innate immunity response Tumor necrosis factor (TNF-α, TNF-β)The TNF is responsible for the initial phase of acute inflammatory response, especially against ...

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Section: Local Anestheticssupporting

confidence: 50%

Anesthesia, cytokines and cancer recurrence

Kitamura¹,

Biaso²,

Ingelmo

et al. 2015

Glob Anesth Perioper Med

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“…Istovremeno, na subcelularnom nivou deluje antinflamatorno, inhibirajući stvaranje proinflamatornih citokina inhibicijom sekretorne aktivnosti B-limfocita 30 . Lidokain se vrlo uspešno primenjuje u tretmanu hroničnog neuropatskog bola, koji se karakteriše ushodnom regulacijom broja natrijumovih kanala (slika 3).…”

Section: Lidokainunclassified

Old drugs are new again (drugs)

Jovičić¹,

Gvozdić²,

Volaš³

et al. 2017

Serb J Anes Inten Therap

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Sažetak UvodS obzirom na to da je akutni bol praiskonski zaštit-ni simptom, a da je hronični bol označen kao bolest savremenog čoveka, zbrinjavanje obe vrste bola, prema Montrealskoj deklaraciji, predstavlja osnovno pravo svakog čoveka i etički imperativ 1 . U eri dobro razvijene farmaceutske industrije, postoji ogroman pritisak društva za proizvodnju novih grupa farmakoloških sredstava u cilju tretiranja bolnih stanja.Osnovna mana novih grupa lekova je nedovoljno poznati spektar neželjenih dejstava, koji se otkriva nakon dovoljno duge upotrebe u praksi. Kako navodi Pharmacy Times iz 2011. godine 2 , za dobijanje odobrenja od Federal drug administration (FDA) za plasiranje novog leka na tržište, potrebno je ogromno finansijsko ulaganje i prelazak dugog puta u sprovođenju pretkliničkih i kliničkih istraživanja. Na primer, 1996. godine, 53% podnetih zahteva za sprovođenje kliničkog istraživanja bilo je odobreno od strane FDA, za razliku od 19% zahteva koliko je bilo podržano 2009. godine 3 . Taj trend se i dalje održava. Ono što je preporuka ovih autora je da se stari, već dobro poznati farmakološki profil lekova proširi novim indikacionim područjem (eng. prepurposing) i da se poznate farmakokinetske i farmakodinamske osobine iskoriste za unapređenje formulacije leka (eng. preformulation). Kroz navedena dva procesa, prolaze neki od najmoćnih medikamenata iz palete multimodalnog pristupa terapiji bola.Kako navode Wu i saradnici, multimodalni pristup lečenju akutnog postoperativnog bola, koji obuhvata i upotrebu modulatora bola, terapijski je pristup koji bi poboljšao kontrolu bola i smanjio potrebu za primenom opioida 4 . Međutim, problematika koju ističu ovi autori se odnosi na širok dijapazon primenjenih doza istog leka, kombinaciju različitih tehnika u različitoj vrsti hirurgije, a sve to ne stvara podlogu za formiranje jednog konzistentnog zaključka. Nasuprot ovom podatku, u tertmanu hroničnog nemalignog bola, primena multimodalnog pristupa i modulatora bola je neophodan terapijski pristup s obzirom na komplek-

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“…7 Alternatively, lidocaine may affect other components of chronic inflammation in GVHD such as collagen secretion, lymphocyte traffic, cytokine production or release, and neutrophil or macrophage activation. 10 The above-mentioned benefits of lidocaine i.v. pulses in systemic sclerosis prompted us to try this therapeutic approach in two patients with severe and refractory skin chronic GVHD secondary to DLI.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of intravenous lidocaine in cutaneous chronic graft-versus-host disease secondary to donor lymphocyte infusion

Ahmed

Paton

et al. 2001

Bone Marrow Transplant

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Summary:We report two cases of refractory chronic graft-versushost disease after donor lymphocyte infusions in which the skin lesions improved dramatically with the use of intravenous pulses of lidocaine. This form of therapy has been used successfully for the cutaneous involvement of scleroderma and may have vasodilator and anti-inflammatory effects. Bone Marrow Transplantation (2001) 28, 97-99. Keywords: chronic GVHD; lidocaine; donor lymphocyte infusion Donor lymphocyte infusion (DLI) is a very promising immunotherapeutic modality of treatment for relapse of malignancy after hematopoietic stem cell transplantation (HSCT) (reviewed in Ref. 1). However, it is associated with significant morbidity and mortality due to marrow aplasia and graft-versus-host disease (GVHD). In a survey of 140 patients treated with DLI for relapse of a variety of malignant diseases in 25 North American centers 75 of 125 (60%) evaluable patients developed acute GVHD (28 with grades III or IV) and 51 out of 84 (61%) developed chronic GVHD (24 with limited and 27 with extensive forms). 2 In another series of 22 patients with chronic myelogenous leukemia, nine (41%) developed chronic GVHD (five limited, four extensive forms). 3 In the first study there was a correlation between clinical response to DLI and development of acute and chronic GVHD, while in the latter one low doses of DLI could induce a graft-versus-leukemia effect without GVHD.Chronic GVHD associated with allogeneic HSCT or DLI seems to have a similar clinical picture 4 and may cause significant disability and deterioration of quality of life, in part because of sclerodermatous skin changes leading to severe contractures. 5 These lesions are poorly responsive to conventional immunosuppression or to alternative therapies for GVHD such as thalidomide, mycophenolate mofetil and tacrolimus, etretinate, PUVA (psoralen plus ultraviolet irradiation) and extracorporeal phototherapy. Spontaneously occurring systemic sclerosis shares the autoimmune pathophysiology and poor treatment response with chronic GVHD 6 and local anesthetics were one of many treatments attempted for the skin manifestations of systemic sclerosis. 7 We report here two cases of sclerodermatous cutaneous chronic GVHD after DLI, which responded dramatically to intravenous administration of lidocaine. Case reports Patient 1The first patient, an 11-year-old boy, received an HLAidentical bone marrow transplantation donated by his sister at the University Hospital of the School of Medicine of Ribeirão Preto, Brazil in September 1995 for an acute biphenotypic leukemia in first complete remission. The conditioning regimen was busulfan 16 mg/kg and cyclophosphamide 120 mg/kg and GVHD prophylaxis was methotrexate plus cyclosporine. The early post-transplant course was uneventful without acute GVHD and with establishment of full donor chimerism (100% XX). At day +530 post-transplant hematologic relapse was detected in the bone marrow (17% blasts). An infusion of donor peripheral blood lymphocytes containing 1.13 × 10 8 T c...

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Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB₄ release and IL‐1 secretion in vitro

Cited by 133 publications

References 41 publications

Anesthesia, cytokines and cancer recurrence

Anesthesia, cytokines and cancer recurrence

Old drugs are new again (drugs)

Beneficial effect of intravenous lidocaine in cutaneous chronic graft-versus-host disease secondary to donor lymphocyte infusion

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Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB4 release and IL‐1 secretion in vitro

Cited by 133 publications

References 41 publications

Anesthesia, cytokines and cancer recurrence

Anesthesia, cytokines and cancer recurrence

Old drugs are new again (drugs)

Beneficial effect of intravenous lidocaine in cutaneous chronic graft-versus-host disease secondary to donor lymphocyte infusion

Contact Info

Product

Resources

About

Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB₄ release and IL‐1 secretion in vitro