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Anaesthetics and immune function.

Surgical trauma and anaesthetics may cause immune suppression, predisposing patients to postoperative infections. Furthermore, stress such as surgery and pain per se is associated with immune suppression which, in animal models, leads to an increased susceptibility to infection and tumour spread. Thus, by modulating the neurohumoral stress response, anaesthesia may indirectly affect the immune system of surgical patients. In particular, regional anaesthesia attenuates this stress response and the associated effects on cellular and humoral immunity. Additionally, anaesthetics may directly affect the functions of immune-competent cells. However, the reported effects of commercial preparations of, for example, propofol, etomidate and midazolam are highly dependent on the applied solvent. Immunosuppressive effects may be particularly relevant in the intensive care unit when anaesthetics are used as long-term sedatives. There is a striking body of evidence that long-term exposure to certain sedatives is paralleled by infectious complications. On the other hand, anti-inflammatory effects of anaesthetics may be therapeutically beneficial in distinct situations such as those involving ischaemia/reperfusion injury or the systemic inflammatory response syndrome. Consequently, sedatives should be administered with careful regard to their respective potential immunomodulatory properties, the clinical situation, and the immunity status of the critically ill patient.

Journal Article↗

Effect of surgical stress on immune function in patients with urologic cancer.

BACKGROUND: To determine the immunosuppressive effect of surgery for urologic cancers, multiple variables of immune function were measured serially before and after operation in patients with urologic cancer. METHODS: Peripheral blood was obtained before operation and at postoperative day 7 and 14 from 20 patients with bladder cancer, renal pelvic, or ureteral cancer, or renal cell carcinoma. RESULTS: In patients with bladder cancer who were undergoing radical cystectomy with use of intestine for urinary diversion, the serum level of immunosuppressive acidic protein (IAP) increased, and serum levels of immunoglobulin (Ig)A, IgG, and IgM decreased after operation. In contrast, the number of CD25+ lymphocytes significantly increased. Transurethral resection of bladder cancer also resulted in an increase in serum IAP level, however, the number of CD4+ and human leukocyte-associated HLA-DR+ lymphocytes increased. In patients with renal pelvic or ureteral cancer undergoing nephroureterectomy with cuff, the level of serum IAP increased and serum IgG level decreased after operation. By contrast, the number of CD3+ lymphocytes increased. In patients with renal cell carcinoma, radical nephrectomy led to a significant increase in the number of CD8+ lymphocytes. CONCLUSIONS: These findings suggest that surgical stress in patients with urologic cancer may result in both suppression and stimulation of host immunity.

Adult↗

Micronutrients in women's health and immune function.

Lawrence J. Machlin's contributions to elucidating the roles of nutrients in optimizing human health included the support of research in the areas of women's health and immune function. Several essential nutrients have been shown to affect women's health throughout the different life stages. Symptoms of premenstrual syndrome affect the vast majority of menstruating women, and calcium supplementation significantly reduces physical and emotional symptoms. Premenstrual syndrome in fact might be a predictor of osteoporosis induced by low calcium intake. Periconceptional multivitamin supplementation has reduced the risk of serious birth defects, premature delivery, and low birth weight by 50% and improved maternal health during pregnancy. Micronutrients of particular importance for prevention of adverse pregnancy outcomes are folic acid, zinc, and iron. However, if the preterm delivery is caused by preeclampsia, then data suggest that calcium supplementation and high doses of vitamins C and E significantly reduce that risk. Well-controlled studies consistently have shown that calcium supplementation, with or without vitamin D, significantly reduces the risk of hip fracture. Antioxidants such as vitamins C and E have been shown to reduce the risk of fracture in women smokers. As in the rapidly growing embryo, the immune system includes rapidly multiplying cells whose functions are dramatically affected by an individual's micronutrient status. Multivitamins have been shown to enhance many aspects of immune response, and antioxidant micronutrients consistently have been found to enhance lymphocyte-proliferative responses and skin-test responses, especially in the elderly.

Adult↗

Effect of packed red cell and whole blood transfusion on liver-associated immune function.

In order to clarify the effect of allogeneic blood transfusion on liver metastases from primary cancer, liver-associated immune function after blood transfusion was evaluated in a murine model. Hepatic sinusoidal lymphocytes (HSL) were strongly cytotoxic to conventional natural killer cell-sensitive target (YAC-1), as well as to natural killer cell-resistant solid adenocarcinoma cells (colon 26), compared with splenic lymphocytes. Allogeneic whole blood transfusion strikingly suppressed the cytotoxic activities of HSL. Red blood cell transfusions also suppressed cytotoxicity to the same degree. In an animal model, allogeneic transfusion increased the rate of liver metastases. Flow cytometric analysis showed that transfusion caused a temporary decrease in the class II antigen positive cell fraction, mainly Kupffer's cells. This phenomenon occurred in parallel with changes in hepatic antitumor activity, indicating the possible importance of the involvement of Kupffer's cell in the development of the killer activity of HSL. These results suggest that blood transfusion may be a significant risk factor for hepatic metastasis by transiently suppressing the immunocompetence of the liver.

Animals↗

Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors.

The objective was to determine the effects of exercise training on changes in blood immune function in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n=25) or control group (n=28). The exercise group trained on cycle ergometers three times per week for 15 wk. The control group did not train. The primary end point was change in natural killer cell cytotoxic activity in isolated peripheral blood mononuclear cells. Secondary end points were changes in standard hematological variables, whole blood neutrophil function, the phenotypes of isolated mononuclear cells, estimations of unstimulated and phytohemaglutinin-stimulated mononuclear cell function (rate of [3H]thymidine uptake), and the production of proinflammatory [interleukin (IL)-1alpha, tumor necrosis factor-alpha, IL-6] and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-beta1). Statistical tests were two-sided (alpha <0.05). Fifty-two participants completed the trial. Intention-to-treat analyses, which included the baseline value as a covariate, showed significant differences between groups for change in percent specific lysis of a target natural killer cell at all five effector-to-target ratios (adjusted mean between-group change over all 5 effector-to-target ratios = +6.34%; P <0.05 for all comparisons), the lytic activity per cell (adjusted mean between-group change = -2.72 lytic units; P=0.035), and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes (adjusted mean between-group change = +218 per dpm x 10(6) cells; P = 0.007). There were no significant differences between groups for change in any other end point. Exercise training increased natural killer cell cytotoxic activity and unstimulated [3H]thymidine uptake by peripheral blood lymphocytes in postmenopausal breast cancer survivors.

Breast Neoplasms↗

Effect of a dietary n-6 polyunsaturated fatty acid supplement on distinct immune functions of goats.

The aim of this study was to investigate whether dietary n-6 polyunsaturated fatty acids (PUFA) alter immune functions as lymphocyte blastogenesis, expression of lymphocyte and monocyte markers, and cell adhesion molecules of the integrin family in goats. Dutch White castrated male goats received a diet either rich in olive oil (control group, n = 4) or rich in corn oil (test group, n = 4) over a period of 3 weeks. The animals in the test group had significantly higher linoleic acid (LA, 18:2n-6) levels in plasma on days 7, 14 and 21 of the diet than control animals. This was also true for washed erythrocyte membranes at day 21. A significant reduction in the percentage of alpha-4 integrin (CD49d) expressing lymphocytes was observed in goats fed LA rich corn oil at day 21. However, no changes were observed in either lymphocyte proliferative responses to ConA and PHA or the expression of other lymphocyte/monocyte markers. In conclusion, feeding corn oil rich in LA caused significant increases in the proportion of LA in the fatty acid composition of plasma and erythrocyte membranes and was accompanied by a significant decrease of the adhesion molecule alpha-4 integrin (CD49d) on lymphocytes but not on monocytes.

Animals↗

Immune function in sarcoidosis. Studies on delayed hypersensitivity, B and T lymphocytes, serum immunoglobulins and serum complement components.

An assessment of immune function was performed in twenty-four patients with recently diagnosed active sarcoidosis. Four patients manifested skin anergy to four antigens. All subjects except one were capable of generating a positive skin response to a croton oil patch test. The incorporation of [3H]thymidine by lymphocytes in vitro in response to the nonspecific mitogens--phytohaemagglutinin, pokeweed mitogen and Con A did not differ between anergic and non-anergic thymidine incorporation in vitro when stimulated by the specific antigens, streptokinase/streptodornase or Candida albicans. Lymphocytes obtained from nine of eleven patients having positive delayed hypersensitivity skin reactions demonstrated MIF production in vitro upon specific antigen challenge. Quantities of circulating B and T lymphocytes did not differ between anergic and absolute numbers of circulating B and T lymphocytes, as well as hypercomplementaemia and hypergammaglobulinaemia when compared to the control group.

B-Lymphocytes↗

Immune function in the elderly.

Normal aging is accompanied by diverse changes in the immune system. Altered function of both T- and B-cells can be shown by losses in proliferative ability and interleukin-2 and interferon synthesis. Granulocyte function is decreased. Although there can be elevations in immunoprotein levels, antibody formation is decreased in most elderly individuals. Response to immunization varies greatly in the aged. This paper discusses the changes in immune function in the elderly, and the clinical implications of these changes.

Aged↗

Cellular immune functions in patients with primary hyperparathyroidism: effects of histamine and cimetidine.

The possibility of a link between parathyroid hyperfunction and cellular immune functions was studied in primary hyperparathyroid (1 degree HP) patients. The effect of cimetidine on lymphocyte functions in 1 degree HP patients and control subjects was also investigated. Histamine-induced suppressor activity of lymphocytes from 1 degree HP patients was significantly greater than that of controls. Cimetidine addition to both normal and 1 degree HP lymphocyte cultures abolished histamine-induced suppression. In vivo administration of cimetidine, while ineffective towards normal lymphocytes, depressed phytohemagglutinin stimulation of 1 degree HP lymphocytes, indicating possible immunological damage caused by this drug, which is frequently used in the treatment of patients with 1 degree HP.

Cimetidine↗

Cellular immune function in patients with cancer of the upper part of the gastrointestinal tract.

Lymphocytes of 30 patients were examined for cellular immune function one day prior to operation. In 11 patients the tests were repeated six weeks after surgery. In comparison with 26 healthy blood donors the E rosette values were strongly reduced in the patients group. The zymosan-complement rosette counts were significantly lower if percentages were compared, but not significant when they were expressed in absolute numbers. Lymphocyte transformation tests revealed significant differences between the patients and control cases with all three mitogens applied (PHA, ConA, PWM). In the 11 patients with the tests repeated after operation, the effect of autologous plasma on the cultures was also studied. The main tendency was inhibition but in some cases the patients' plasma enhanced the reaction. Killer cell activity by ADCC was significantly lower in patients' than in the healthy donors' lymphocytes in different target-effector cell ratios.

Animals↗

Comparison between the effects of sigma receptor ligand JO 1784 and neuropeptide Y on immune functions.

Recent evidence suggests that sigma receptor ligands and neuropeptide Y may act through the same pathways to modulate centrally mediated immune function. The present study demonstrated that both the sigma receptor ligand igmesine: (+)-N-cyclopropylmethy-N-methyl-1, 4-diphenyl-1-yl-but-3-en-1-ylamine, hydrochloride (JO 1784) (10(-7) and 10(-5) M) and neuropeptide Y (10(-9) and 10(-7) M) in vitro significantly reduced neutrophil phagocytosis and decreased mitogen stimulated lymphocyte proliferation. By contrast, central administration of JO 1784 (0.5 and 5 microg/5 microl) significantly reduced the activity of neutrophil phagocytosis, but enhanced lymphocyte proliferation without changing the serum concentration of corticosterone. Neuropeptide Y (10(-9) and 10(-7) M), following intracerebroventricular infusion, also decreased the neutrophil response, but significantly raised the corticosterone concentration. These results indicate that different mechanisms (involving various neurotransmitters and their receptors, changes in the activity of the hypothalamic-pituitary-adrenal axis, or sigma receptor subtypes) may be involved in the central effects of JO 1784 and neuropeptide Y.

Animals↗

[Comparative study on effect of Tripterygium polyglycosides on mucous immune function of rat models of arthritis induced by collagen II and by adjuvant].

OBJECTIVE: To observe the effects of Tripterygium polyglycosides (TWP) on mucous immune function in rat models of arthritis induced respectively with collagen-II induced arthritis (CIA) & adjuvant arthritis (AA). METHODS: CIA and AA model rats were induced by immunization with collagen II emulsified with complete Freund's adjuvant and complete Freund's adjuvant respectively and treated with TWP. Rats' mucus, systemic immunological indexes (peripheral subsets of T cells), local inflammatory factors (IL-6, TNF-alpha, COX-2,and NF-kappaB, etc. ) were observed. RESULTS: In CIA model group, CD4+ in Peyer's Patch (PP), peripheral CD4+ and CD8+ positive T cells all raised, while in the AA model group, CD4+ lowered and CD8+ raised on PP, with both subsets increased. Effects of TWP on T lymphocyte subsets in PP and blood of the two models were different. High leveled IL-6, TNF-alpha, COX-2 and NF-kappaB expression could be seen in both model groups, and these inflammatory media could be inhibited by TWP. CONCLUSION: There exist similarities and differences between the two models in aspects of mucus immune response and effect of TWP on them.

Animals↗

Tumor necrosis factor, natural killer activity and other measures of immune function and inflammation in elderly men with heart failure.

OBJECTIVE: To determine the status of tumor necrosis factor (TNF) and other measures of immunity and inflammation in chronic heart failure (CHF) in the elderly. DESIGN: Comparative survey study of subjects with heart failure and age-matched controls. SETTINGS: University affiliated tertiary care VA Medical Center, Heart Failure Clinic. PATIENTS: Twenty men with New York Class II and III heart failure and 17 age-matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Levels of lymphocyte mitogenesis, TNF, natural killer (NK) cell activity, elastase-alpha 1-antitrypsin (E/alpha) and cross-linked fibrin D-dimers (XDP). RESULTS: TNF levels (p = 0.27), NK activity (p = 0.56), and lymphocyte mitogenesis (p = 0.67) were similar in patients and controls. E/alpha levels were somewhat lower in CHF patients (p = 0.05) and XDP were similar (p = 0.59). However, TNF levels were significantly related to NK activity and to E/alpha activity in elderly men with heart failure but not controls. XDP were positively related to NK in heart failure patients but not controls. CONCLUSION: TNF and other measures of immune function and inflammation do not appear to be significantly elevated in elderly patients with heart failure of moderate severity. However, significant relationships exist between TNF, NK activity, XDP and E/alpha in the heart failure patients only, suggesting that immune activation and subclinical inflammation does exist in these patients.

Aged↗

Depression and immune function: central pathways to morbidity and mortality.

OBJECTIVE: The increased morbidity and mortality associated with depression is substantial. In this paper, we review evidence suggesting that depression contributes to disease and death through immune dysregulation. METHOD: This review focuses on recent human studies addressing the impact of depression on immune function, and the health consequences of those changes. RESULTS: There is growing evidence that depression can directly stimulate the production of proinflammatory cytokines that influence a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. Additionally, depression can down-regulate the cellular immune response; as a consequence, processes such as prolonged infection and delayed wound healing that fuel sustained proinflammatory cytokine production may be promoted by depression. CONCLUSIONS: These direct and indirect processes pose the greatest health risks for older adults who already show age-related increases in proinflammatory cytokine production. Thus, aging interacts with depression to enhance risks for morbidity and mortality.

Aging↗

Disclosure of HIV status to medical providers: differences by gender, "race," and immune function.

OBJECTIVE: The authors used data from a larger study to explore differences by gender, self-reported racial identification, and immune function in disclosure of HIV-positive serostatus to medical providers (dentists, family doctors, and emergency room [ER] and obstetrics-gynecology [ob/gyn] providers). METHOD: The authors analyzed interview responses from a convenience sample of African American and white men and women receiving HIV medical care at urban hospitals and clinics in St. Louis. Missouri. RESULTS: Of 179 respondents using at least one of three types of providers, 124 (69%) disclosed their HIV status to all applicable types of providers, 39 (22%) disclosed to only one or two types of providers, and 16 (9%) did not disclose to any of these types of providers. "Race" and CD4 count, but not gender, were independently associated with disclosure to dentists, family doctors, and ER providers in multivariate logistic regression analyses. CONCLUSIONS: Differences in disclosure rates, especially among patients who may be asymptomatic, suggest a need for public health education of both medical providers and patients with HIV.

Adolescent↗

[Effect of acupuncture-drug compound anesthesia on alteration of immune function in patients undergoing open-heart surgery].

OBJECTIVE: To observe the effect of electro-acupuncture (EA) on alteration of immune function of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB), and to appraise the value of acupuncture-drug compound anesthesia in the operation. METHODS: Thirty patients undergoing atrial septal defect repairing operation were selected and divided into three groups, Group A was the general anesthesia group; Group B, the acupuncture anesthesia group and Group C, the general anesthesia plus EA group. Peripheral venous blood of patients was collected at different time points, i.e. before anesthesia, before CPB, 30 min and 24 hrs after CPB, to determine natural killer cells activity (NKCA), and the levels of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in supernatant of cell culture were also tested. RESULTS: NKCA was significantly lowered in Group A before CPB but increased in Group B, while no evident change was found in Group C, so the level of NKCA in Group B was significantly higher than in the other two groups. It lowered in all the three groups after CPB, especially evidently in Group B, so as to cause the NKCA level in Group B lower than that in Group A. The lowering further progressed, 24 hrs after CPB, NKCA in Group B was more reduced than that in Group C. Levels of IFN-gamma and IL-2 lowered in all the three groups after CPB, and further lowered at time point of 24 hrs after CPB, but the parameters in Group C were significantly higher than those in Group B. CONCLUSION: EA could enhance NKCA, but acupuncture anesthesia couldn't inhibit the suppressive effect of CPB on NKCA, IL-2 and IFN-gamma, suggesting that the immunosuppression induced by stress has a prior effect. General anesthesia plus EA yielded better effect than general anesthesia and acupuncture anesthesia, but it could't improve the immunosuppression completely, indicating that the compound anesthesia could partially improve the immunosuppression induced by CPB.

Acupuncture Analgesia↗

In vivo effects of maternal immunosuppression during pregnancy on the immune function of newborn infants.

When used in pregnancy, immunosuppressants can cross the placental barrier and enter foetal circulation, possibly affecting the immune system of the foetus. This study evaluated the immune function in eight children born by mothers with connective tissue diseases who received immunosuppressants (cyclosporine A or dexamethasone) during pregnancy and in six babies from mothers with similar diseases, but who did not receive any treatment. Judging by the cytokine production of interleukin-2 and interferon-gamma in peripheral blood mononuclear cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin, immunosuppressive drugs given for rheumatic disorders during pregnancy do not induce significant immunosuppression in babies.

Connective Tissue Diseases↗

[Effects of radix Astragali injection on apoptosis of lymphocytes and immune function in patients with systemic lupus erythematosus].

OBJECTIVE: To investigate the effect of Radix Astragali Injection on apoptosis of lymphocytes and immune function in treating patients with systemic lupus erythematosus (SLE). METHODS: Eighty SLE patients were randomly assigned into the routine treatment group (RT) treated with conventional therapy and the Radix Astragali treated group (RA) treated with Radix Astragali Injection besides routine treatment. The expressions of Fas and Bcl-2 antigen on lymphocytes and the changes of T lymphocyte subsets in peripheral blood before and after treatment were observed. RESULTS: After treatment, the expression of Fas antigen on lymphocytes significantly lowered (P < 0.01), and that of Bcl-2 antigen, CD4+ lymphocyte subset and CD4+ / CD8+ ratio significantly increased in both groups (all P < 0.01). However, the changes of Fas antigen expression, CD4+ and CD4+ / CD8+ ratio were more significant in the RA group than those in the RT group (P < 0.05). CONCLUSION: Radix Astragli Injection can enhance the inhibitory function of corticosteroid/immunosuppressant on apoptosis, and regulate the ratio and function of T lymphocyte subsets to normal range, which may be a useful approach for enhancing the efficacy of treatment to SLE.

Adolescent↗