Anesthesia, cytokines and cancer recurrence

Abstract

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 ...

Antitumor Anesthetic Strategy in the Perioperatory Period of the Oncological Patient: A Review

“…The term "intravenous anesthetics" includes substances with anesthetic properties that are not gases and that are administered intravenously (41). Intravenous anesthesia was used in 1930, with the introduction of barbiturates, and these drugs are currently considered essential in deep sedation and general anesthesia, whether balanced with the use of inhaled agents, or total intravenous anesthesia (46).…”

“…When investigating the link between this anesthetic and the inflammatory response, significant results were obtained; thanks to their inhibitory effect on cyclooxygenase 2 (COX-2). There is less production of PGE 2 by human monocytes in vitro, (53) and it decreases the concentration of other proinflammatory cytokines, such as IL-10, IL-6, or tumor necrosis factor α (TNF-α) (46). Due to all the mentioned mechanisms, propofol generates a lower inflammatory response when compared to inhaled agents, which could improve the oncological prognosis of patients (53).…”

Regional anaesthesia in breast cancer: Benefits beyond pain

“…[ 4 6 ] Volatile anaesthetics have been reported to induce carcinogenic effects through impact on hypoxia-inducible factors and insulin-like growth factors, both of which are potentiated by the use of volatile anaesthetics. [ 12 13 ] Sevoflurane induces cell motility and invasion by reduction of matrix metalloproteinase (MMP)-2 and MMP-9126, and xenon inhibited migration in breast adenocarcinoma acells. [ 14 ] However, conflicting data exist about volatile anaesthetics as well.…”

Perioperative effects of co-administration of tci propofol combined with clonidine and ketamine

“…These changes are caused by afferent neuronal stimulus from the area of surgery, cytokines release from tissue damaged by trauma, and activation of cellular and humoral immune pathways. 1,2 Both general and regional anesthesia help to suppress the stress response due to surgical trauma. This happens because anesthesia provides sympathetic and afferent nerve fibers block that modulate the pituitary-adrenocortical system.…”