Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942012000500010
Brazilian Journal of Anesthesiology
Review Article

Opioides e o sistema imunológico: relevância clínica

Opioids and the immune system: clinical relevance

João Batista Santos Garcia; Mirlane Guimarães de Melo Cardoso; Maria Cristina Dos-Santos

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Resumo

JUSTIFICATIVA E OBJETIVO: O crescente uso de opioides para o tratamento da dor é uma realidade em vários países. Com o aumento do uso aparecem questionamentos menos usuais, como a influência dos opioides nas respostas imunológicas. O presente estudo tem como objetivo detalhar a resposta imunológica explorando as influências dos efeitos dos opioides sobre a resposta inflamatória em situações experimentais e clínicas, bem como sua importância para a prática diária. CONTEÚDO: Após revisão de artigos publicados em revistas indexadas no Medline, foi descrita a resposta imunológica de forma geral, especialmente em seu aspecto celular. Após essa abordagem, foram identificados os mecanismos de liberação dos opioides endógenos e a modulação da resposta imune aos opioides exógenos na dor aguda e crônica, sempre finalizando com as implicações clínicas e sua aplicabilidade na rotina de atendimento. CONCLUSÕES: Embora vários estudos apontem para um efeito imunodepressor dos opioides, a relevância clínica dessas observações continua incerta e serve apenas como um prerrequisito para que novas investigações nessa área sejam conduzidas. Recomendações definitivas para a aplicação de opioides, nas mais variadas situações da prática clínica em relação às consequências imunológicas desses fármacos, ainda não podem ser dadas até o momento presente.

Palavras-chave

ANALGÉSICOS, Opioides, DOR, SISTEMA IMUNOLÓGICO

Abstract

BACKGROUND AND OBJECTIVES: The increasing use of opioids for pain treatment is a reality in several countries and, therefore, unusual questions arise, such as the influence of opioids on immune responses. The present study aims to detail the immune response by exploring the influences of opiate effects on inflammatory response in experimental and clinical situations, as well as its importance in daily practice. CONTENT: After reviewing the articles published in journals indexed in Medline, we found that immune response has been generally described, especially regarding its cellular aspect. Following this approach, we identified the mechanisms of endogenous opioid release, modulation of immune response to exogenous opioids in acute and chronic pain, always ending with the clinical implications and applicability in routine care. CONCLUSIONS: Although several studies point to an immunosuppressive effect of opioids, the clinical relevance of these observations remains uncertain and only serves as a prerequisite for further investigations in this area. Definitive recommendations for the use of opioids in various situations of clinical practice regarding the immunological consequences of these drugs still cannot be provided until the present moment.

Keywords

Analgesics, Opioids, Immune System, Pain

References

Sacerdote P. Opioids and the immune system. Palliat Med. 2006;20:9-15.

Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801.

Yoneyama M, Fujita T. RNA recognition and signal transduction by RIG-I-like receptors. Immunol Rev. 2009;227:54-65.

Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology. 2010;11(5):373-384.

Abraham SN, St. John AL. Mast cell-orchestrated immunity to pathogens. Nature Reviews Immunology. 2010;10(6):440-452.

Paust S, von Andrian UH. Natural killer cell memory. Nature Immunoly. 2011;12(6):500-508.

Zhu J, Yamane H, Paul W E. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445-489.

Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003;9:1003-1008.

Stein C, Zollner C. Opioids and sensory nerves. Pharmacology of Sensory Nerves, Handbook of Experimental Pharmacology. 2009.

Vetter I, Kapitzke D, Hermanussen S, Monteith GR, Cabot PJ. The effects of pH on beta-endorphin and morphine inhibition of calcium transients in dorsal root ganglion neurons. J Pain. 2006;7:488-499.

Mousa SA, Shakibaei M, Sitte N, Schafer M, Stein C. Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology. 2004;145:1331-1341.

Machelska H, Schopohl JK, Mousa SA, Labuz D, Schafer M, Stein C. Different mechanisms of intrinsic pain inhibition in early and late inflammation. J Neuroimmunol. 2003;141:30-39.

Hollt V. Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol. 1986;26:59-77.

Stein C, Lang JL. Peripheral mechanisms of opioid analgesia. Curr Opin in Pharmacol. 2009;9:3-8.

Brack A, Rittner HL, Machelska H, Leder K, Mousa SA, Schafer M, Stein C. Control of inflammatory pain by chemokine-mediated recruitment of opioid-containing polymorphonuclear cells. Pain. 2004;112:229-238.

Rittner HL, Lux C, Labuz D, Mousa SA, Schafer M, Stein C, Brack A. Neurokinin-1 receptor antagonists inhibit the recruitment of opioidcontaining leukocytes and impair peripheral antinociception. Anesthesiology. 2007;107:1009-1017.

Machelska H, Mousa SA, Brack A. Opioid control of inflammatory pain regulated by intercellular adhesion molecule-1. J Neurosci. 2002;22:5588-5596.

Hermanussen S, Do M, Cabot PJ. Reduction of beta-endorphincontaining immune cells in inflamed paw tissue corresponds with a reduction in immune-derived antinociception: reversible by donor activated lymphocytes. Anesth Analg. 2004;98:723-729.

Rittner HL, Labuz D, Schaefer M. Pain control by CXCR2 ligands through Ca2+- regulated release of opioid peptides from polymorphonuclear cells. FASEB J. 2006;20:2627-2629.

Machelska H, Stein C. Immune mechanisms in pain control. Anesth Analg. 2002;95:1002-1008.

Stein C, Pfluger M, Yassouridis A. No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia. J Clin Invest. 1996;98:793-799.

Stein C, Comisel K, Haimerl E. Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med. 1991;325:1123-1126.

Stein C, Hassan AHS, Lehrberger K. Local analgesic effect of endogenous opioid peptides. Lancet. 1993;342:321-324.

Page GG. Immunologic effects of opioids in the presence or absence of pain. J Pain Symp Manag. 2005;29:S25-31.

Singhal P, Kapasi A, Reddy K, Franki N. Opiates promote T cell apoptosis through JNK and caspase pathway. Adv Exp Med Biol. 2002;493:127-135.

Singhal PC, Sharma P, Kapasi AA. Morphine enhances macrophage apoptosis. J Immunol. 1998;160:1886-1893.

Singhal PC, Kapasi AA, Reddy K. Morphine promotes apoptosis in Jurkat cells. J Leukoc Biol. 1999;66:650-658.

Mellon RD, Bayer BM. Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action. J Neuroimmunol. 1998;83:19-28.

Flores LR, Dretchen KL, Bayer BM. Potential role of the autonomic nervous system in the immunosuppressive effects of acute morphine administration. Eur J Pharmacol. 1996;318:437-446.

McCarthy L, Wetzel M, Sliker JK. Opioids, opioid receptors, and the immune response. Drug Alcohol Depend. 2001;62:111-123.

Sacerdote P, Manfredi B, Mantegazza P, Panerai AE. Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol. 1997;121:834-840.

Schneemilch CE, Schilling T, Bank U. Effects of general anaesthesia on inflammation. Best Pract Res Clin Anaesthesiol. 2004;18:493-507.

Walters I. Opioids and immunosuppression: clinical relevance. Anaesthetist. 2003;52:442-452.

Shavit Y, Terman GW, Lewis JW. Effects of footshock stress and morphine on natural killer lymphocytes in rats: studies of tolerance and crosstolerance. Brain Res. 1986;372:382-385.

Shavit Y, Martin FC, Yirmiya R. Effects of single administration of morphine or footshock stress on natural killer cell cytotoxicity. Brain BehavImmun. 1987;1:318-328.

Coussons-Read ME, Giese S. Acute morphine treatment alters cellular immune function in the lungs of healthy rats. Int Immunopharmacol. 2001;1:1571-1581.

Flores LR, Wahl SM, Bayer BM. Mechanisms of morphine-induced immunosuppression: Effect of acute morphine administration on lymphocyte trafficking. J Pharmacol Exp Ther. 1995;272:1246-1251.

Lysle DT, Coussons ME, Watts VJ. Morphine-induced alterations of immune status: dose dependency, compartment specificity and antagonism by naltrexone. J Pharmacol Exp Ther. 1993;265:1071-1078.

Bilfinger TV, Fimiani C, Stefano GB. Morphine's immunoregulatory actions are not shared by fentanyl. Int J Cardiol. 1998;64(^s1):S61-S66.

Martucci C, Panerai AE, Sacerdote R. Chronic fentany! or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses. Pain. 2004;110:385-392.

Decker D, Schondorf M, Bidlingmaier F. Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting downregulation of cell-mediated and up-regulation of antibodymediated immunity commensurate to trauma. Surgery. 1996;119:316-325.

Schietroma M, Carlei F, Lezoche E. Evaluation of immune response in patients after open or laparoscopic cholecystectomy. Hepatogastroenterol. 2001;48:642-646.

El Solh AA, Bhora M, Pineda L, Dhillon R. Nosocomial pneumonia in elderly patients following cardiac surgery. Resp Med. 2006;100:729-736.

Spies C, Eggers V, Szabo G. Intervention at the level at the neuroendocrine: immune axis and postoperative pneumonia rate in long-term alcoholics. Am J Respir Crit Care Med. 2006;100:729-736.

Shavit Y, Terman GW, Lewis JW. Effects of footshock stress and morphine on natural killer lymphocytes in rats: studies of tolerance and crosstolerance. Brain Res. 1986;372:382-385.

Bhaskaran M, Reddy K, Sharma S. Morphine-induced degradation of the host defense barrier: Role of macrophage injury. J Infect Dis. 2001;184:1524-1531.

De Waal EJ, Van Der Laan JW, Van Loveren H. Effects of prolonged exposure to morphine and methadone on in vivo parameters of immune function in rats. Toxicol. 1998;129:201-210.

Coussons-Read ME, Daniels M, Gilmour MI. Morphine reduces pulmonary inflammation in response to influenza infection. Life Sci. 1999;65:1141-1152.

Sasamura T, Nakamura S, Iida Y. Morphine analgesia suppresses tumor growthand metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol. 2002;441:185-191.

Yeager MP, Yu CT, Campbell AS. Effect of morphine and betaendorphin on human Fc receptor-dependent and natural killer cell functions. Clin Immunol Immunopathol. 1992;62:336-343.

Weinert CR, Kethireddy S, Roy S. Opioids and infections in the intensive care unit should clinicians and patients be concerned?. J Neuroimmune Pharmacol. 2008;3:218-229.

Schwacha MG, McGwin Jr G, Hutchinson CB, Cross JM, Maclennan PA, Rue LW. The contribution of opiate analgesics to the development of infectious complications in burn patients. Am J Surg. 2006;192:82-86.

Anand KJ, Hall RW, Desai N. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the Neopain randomized trial. Lancet. 2004;363:1673-1682.

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