Opioids in the immune system: from experimental studies to clinical practice

SUMMARY INTRODUCTION: Opioids interact with both innate and adaptive immune systems and have direct effects on opioid receptors located on immune cells. Research on this topic has provided evidence of the opioid influence on the immune response associated with surgical stress. The immunological effects of opioids are currently being investigated, particularly whether they influence the outcome of surgery or the underlying disease regarding important aspects like infection or cancer progression. This review addresses background research related to the influence of the opioid receptor on the immune system, the immunosuppressive effect associated with major opioids during the perioperative period, and their clinical relevance. The objective of the study was to review the effects of opioids on the immune system. Methods: A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "surgical procedures," "analgesics," "opioids" and "perioperative care." Results: The immunosuppressive effect of opioids was identified over 30 years ago. They include signaling and acting directly through immune cells, including B and T lymphocytes, NK cells, monocytes, and macrophages, as well as activating the downstream pathways of the hypothalamic-pituitary-adrenal (HPA) axis leading to the production of immunosuppressive glucocorticoids in the peripheral and sympathetic nervous system.

RESUMO INTRODUÇÃO: Os opioides interagem com ambos os sistemas imunes, inato e adaptativo, através de efeitos diretos sobre os receptores dos opioides localizados nas células imunes. As pesquisas neste assunto têm fornecido evidência da influência dos opioides sobre a resposta imune associada ao estresse cirúrgico. Os efeitos imunológicos dos opioides estão sendo pesquisados na atualidade, principalmente se eles determinam o resultado da cirurgia ou doença consequente devido a fatos importantes como infecção ou progressão do câncer. Essa revisão tem como alvo ver antecedentes em pesquisa relativa à influência dos receptores dos opioides no sistema imunológico, o efeito imunossupressor associado com opioides maiores durante o período peri-operatório e sua importância clínica. O objectivo da pesquisa foi revisar os efeitos dos opioides no sistema imunológico. MÉTODOS: Uma estrategia de procura foi dirigida na mídia PubMed, e no cadastro de Embase e The Cochrane, usando os termos "imunosuppressão", "sistema imunológico", "procedimentos cirúrgicos", "analgésicos", "opioides" e "cuidado peri-operatório". RESULTADOS: O efeito imunosuppressor dos opioides foi identificado há mais de 30 anos. Os efeitos imunosupressores incluem sinalização e ação diretamente através das células imunes, mesmo com os linfócitos B e T, células NK, monócitos e macrófagos, também como ativando as vias de corrente do eixo hipotálamo- hipófise- adrenal (HPA) levando à produção de glucocorticoides imunossupresores no sistema nervoso periférico e simpático.

Inducible protective processes in animal systems XV: Hyperthermia enhances the Ethyl methanesulfonate induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus

Purpose: To understand the role of hyperthermia in adaptive response, Ethyl methanesulfonate [EMS] an anticarcinogenic agent, adapted meiotic cells of Poecilocerus pictus was used

Materials and methods: Based on the pilot toxicity study, the effective higher temperatures of 40[degree sign]C and 45[degree sign]C for 15 or 30 min were chosen. P. pictus were treated with conditioning [L] or challenging [H] doses of EMS and 2 h time lag [TL] between these doses [L-2 h-H] was employed. Different treatment schedules were used to analyze the influence of hyperthermia on EMS induced adaptive response namely [i] pre treatment; [ii] inter treatment; [iii] post treatment and [iv] cross adaptation. After each treatment schedule, animals were sacrificed at 12, 24, 36 and 48 h recovery times, testes were processed for meiotic chromosome preparations and anomalies were analyzed

Results: The frequencies of anomalies induced by both conditioning and challenging doses of EMS were significantly higher [p< 0.05] compared to those of the control and hyperthermia groups. The combined treatments resulted in 44-50% reduction compared to additive effect of EMS. The pre, inter, post and cross adaptation treatments with hyperthermia significantly reduced the frequencies of chromosomal anomalies compared to the challenge and combined treatments with EMS at all recovery times [p< 0.05] tested

Conclusion: There is a protection against EMS induced anomalies by hyperthermia in in vivo P. pictus. As far as our knowledge is concerned, this is the first report to demonstrate that hyperthermia enhances the EMS induced adaptive response in in vivo meiotic cells

Ultrastructural study on biomphalaria alexandrina haemocytes infected with schistosoma mansoni in Egypt and its correlation with nitric oxide level

Some snails of Biomphalaria alexandrina can resist the infection of Schistosoma mansoni so this study aimed to clearly this mechanism by using light and electron microscopy [EM] and determine the role of Nitric oxide in this mechanism. B. alexandrina snails used in this study were exposed individually to S. mansoni infection according to their response they were classified into susceptible group [shed cercariae] and resistant group [failed to shed cercariae]. Snails not exposed to infection were included in this study as control group. Nitric oxide [NO] level was assayed directly in the soluble fraction of B. alexandrina haemolymph supernatants collected from each group of B. alexandrina snails were subjected to NO assay by the Greiss reaction. The level of NO in haemolymph of infected snails was significantly increased [p<0.001] than both control and non infected snails groups, however, in non infected snails group had significantly [p<0.05] compared to control group. This study when correlated the changes recognized by EM with NO level the pro apoptotic effect of high level of NO on the haemocytes. Characterization and identification of cell shape of haemocytes in both haemolymph and tissue were examined by light and electron microscopy. Examination of B. alexandrina snail's haemocytes revealed three types of different cells classified according to their shape and granular contents. These cells are granulocytes, amoe-bocytes and hyalineocytes. Electron microscope Study also revealed the important role of granulocytes and amoebocytes as defense mechanism against snail infection. NO is considered an important anti parasite molecule; intra-molluscan stages of parasites switch off host NO defense response

Modulation of tuberculosis-related immune responses byhelminths

Tuberculosis [TB] continues to be a major worldwide health problem, with 9.4 million newly emerging active tuberculosis cases and causes nearly 2 million deaths annually. Currently, experimental evidence for an strong association between helminths and diminished T helper [Th] l immunity against Mycobacterium tuberculosis infection is based on studies which show that helminth-induced Th2, T regulatory [Treg] responses and alternatively activated macrophages contribute to enhanced susceptibility to TB. In this context, it has been shown that Thl response is reduced in helminth coinfected TB patients. This article discusses what is presently known about the types of immune responses modulated by helminths to diminish the protective immune response to TB

Immunomodulatory effects of betulinic acid from the bark of white birch on mice

The objective of this study was to explore the immunomodulatory effects of betulinic acid (BA) extracted from the bark of white birch on mice. Female mice were orally administered BA for 14 days in doses of 0, 0.25, 0.5, and 1 mg/kg body weight. We found that BA significantly enhanced the thymus and spleen indices, and stimulated lymphocyte proliferation induced by Concanavalin A and lipopolysaccharide as shown by MTT assay. Flow cytometry revealed that BA increased the percentage of CD4+ cells in thymus as well as the percentage of CD19+ and the ratios of CD4+/CD8+ in spleen. BA increased the number of plaque-forming cell and macrophage phagocytic activity as indicated by a neutral red dye uptake assay, and the peritoneal macrophages levels of TNF-alpha were also increased. In contrast, serum levels of IgG and IgM and serum concentrations of IL-2 and IL-6 were significantly decreased in BA-treated mice compared to the control as assayed by haemagglutination tests and ELISA, respectively. Taken together, these results suggest that BA enhances mouse cellular immunity, humoral immunity, and activity of macrophages. Thus, BA is a potential immune stimulator and may strengthen the immune response of its host.