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Suppression of immune function in growth hormone-deficient children during treatment with human growth hormone.

Inasmuch as growth hormone is known to interact with the immune system, we studied immune functions including immunoglobulins, cell surface markers, mitogen responses, and polymorphonuclear cell function in eight children with growth hormone deficiency, ages 1 to 17 years, before and during treatment with human growth hormone for 12 to 16 months. Before treatment immune functions were normal in all children. Treatment with human growth hormone did not significantly affect serum immunoglobulins, polymorphonuclear cell function, or percent T cells. However, percent B cells decreased to subnormal levels in seven of seven patients. T helper/suppressor ratios decreased in all patients, to subnormal values in seven of eight patients; and mitogen responses decreased to below normal in all. The decline of percent B cells was transient in all patients, of T helper/suppressor ratios in seven of eight, and mitogen responses in five of eight patients. In vitro incubation of lymphocytes with growth hormone resulted in no changes in cell surface markers or mitogen responses. Although the depression of immune functions resulted in no increased rate of infections during the observation period, we do not know the possible effects of prolonged treatment and therefore caution against the indiscriminate use of human growth hormone. The effects of biosynthetically obtained growth hormone on immune function remain to be determined.

Adolescent

Protection from guanethidine-induced neuronal destruction by nerve growth factor: effect of NGF on immune function.

The chronic administration of guanethidine causes an immune-mediated destruction of sympathetic neurons in rats. Destruction can be prevented by various immunosuppressive agents, including gamma-irradiation and cyclophosphamide, as well as by administration with nerve growth factor (NGF). Experiments were conducted to determine whether: (1) NGF prevented accumulation of guanethidine within sympathetic neurons; and (2) NGF caused an inhibition of immune function by either blocking proliferation of immune-competent cells or by blocking effector function even in the presence of antigen and activated immune cells. NGF did not prevent accumulation of guanethidine within sympathetic ganglia in vivo, a necessary prerequisite for neuronal destruction, nor was it inhibitory on immune function using several assay systems. NGF, purified by either conventional methods or additionally by HPLC ("ultrapure'), did not inhibit either proliferation of cloned cytotoxic T lymphocytes (CTL) to antigen (class I major histocompatibility antigens) or lysis of target cells bearing the appropriate antigens. In addition, NGF did not exhibit growth stimulating effects in this assay system (i.e. it could not substitute for T cell growth factor). NGF also did not cause an inhibition of either murine or rat allogeneic mixed lymphocyte responses measured by lysis of appropriate target cells or proliferation, respectively. Finally, NGF did not inhibit, but rather appeared to stimulate the antibody response to sheep red blood cells generated in vivo in young rats. Thus NGF does not appear to prevent the immune-mediated neural destruction induced by guanethidine by acting as an immunosuppressive agent, but rather acts by some other mechanism such as preventing expression or recognition of antigen(s) on the sympathetic neuron.

Animals

Immune function in lines of mice selected for high or low degrees of behavioral asymmetry.

Cerebral lateralization has been suggested to play a regulatory role in immune function. In this study, several measures of immune function were evaluated in mice selectively bred for either a strong (HI) or weak (LO) degree of behavioral asymmetry (paw preference) and compared to an unselected control population (HET). Both HI and LO animals had fewer spleen cells but higher degrees of [3H]thymidine incorporation into DNA (on a per cell basis) than HET mice. However, only HI mice had lower immune functions compared to HET controls manifest as reduced mixed leukocyte reaction (MLR), cytotoxic T lymphocyte (CTL) activity, and natural killer (NK) cell activity. These findings indicate that although both extremes in the degree of paw preference may be associated with deviations from the norm, a high degree of behavioral lateralization is associated with decreased immune responsiveness in this animal model.

Animals

Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience&#xa0;postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2&#x2009;mg&#xb7;kg-1&#xb7;h-1 during anesthesia, followed by 1&#x2009;mg&#xb7;kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p&#x2009;=&#x2009;0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p&#x2009;=&#x2009;0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p&#x2009;<&#x2009;0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

Humans

Vitamin E and immune functions.

Vitamin E, the major lipid-soluble antioxidant present in all cellular membranes, is an important nutrient for optimal immune function. When animals are fed nutritionally complete diets lacking vitamin E, immune responses are adversely affected. Supplementation of these diets with higher than nutritionally adequate levels of vitamin E enhances immune responses. High levels of PUFA are immunosuppressive, and vitamin E can partially overcome this immunosuppression. High levels of vitamin C can protect tissue levels of vitamin E and may indirectly contribute to the immunoenhancement by vitamin E. Severe selenium deficiency is immunosuppressive. Vitamin E can protect some aspects of immune responses from the adverse effects of selenium deficiency. These data clearly indicate that nutrients that affect the overall antioxidant status have important effects on immune functions. In addition, antioxidant nutrient interactions can synergize to overcome the adverse effects of polyunsaturated fatty acids on immune functions (Fig 2).

Animals

[Kinetic observation on BRC immune function of patients with epidemic hemorrhagic fever].

The RBC immune function of 88 patients with epidemic haemorrhagic fever (EHF) was examined kinetically with complement-labeled yeast method established by Guo Feng. The results showed that the percentage of RBC c3b receptor rossette, activity of RCIA-enhancing factor and c3 in sera of patients during the 3 different phases of EHF were markedly lower than those of the normal controls, while the percentage of RBC IC rossete, activity of RCIA-inhibiting factor and CIC in sera of the patients were manifestly higher (P less than 0.01). The change of all the indices observed above was most apparent in oliguric phase. This suggested that RBC immune function is lowered in the process of EHF.

Adult

Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia.

Serial in vitro immune function studies of peripheral blood mononuclear cells (PBMC) were carried out during the long-term treatment with recombinant interferon-alpha 2 (IFN-alpha 2) in a patient with hairy-cell leukemia (HCL). Parameters of B- and T-cell functions as well as NK-cell activity were determined. Treatment with IFN-alpha 2 is associated with temporary and long-term depression of some immune functions, but can also normalize immune responses: in vitro-induced immunoglobulin synthesis, which was normal at diagnosis, was inhibited during the first weeks of IFN therapy but subsequently rose to normal levels. Lymphocyte proliferative responses to mitogens and antigens that were markedly reduced pretherapeutically were further depressed by IFN treatment but, with the exception of pokeweed mitogen (PWM)-induced responses, normalized completely by the 15th to 17th week of treatment. Cocultivation of PBMC with monocytes from normal individuals enhanced depressed lymphocyte proliferative responses. NK-cell activity, which was low at diagnosis, did not rise to the normal range during IFN treatment, but rapidly normalized when IFN therapy was stopped. A discussion is presented on the implications of the alteration of immune functions by treatment with IFN.

Antibody Formation

The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial.

Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p less than 0.05), T4 subsets (p less than 0.05), T4 to T8 ratio (p less than 0.01) and the proliferation of lymphocytes in response to phytohaemagglutinin (p less than 0.01). In contrast, no significant changes were noted in the immune function of the placebo group. We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients.

Aged

Effect of thyroxine and chicken growth hormone on immune function in autoimmune thyroiditis (obese) strain chicks.

The effect of thyroxine (T4) and/or recombinant chicken growth hormone (rcGH) supplementation on immune function and on immune cell maturation was examined in Obese strain chickens. Day-old Obese strain chicks received the control treatments or were treated with either T4 (supplemented in the diet), T4-rcGH, or rcGH (by daily injection) in a full factorial design. At 4 weeks of age, the proliferative activity of peripheral blood T cells to either mitogenic or allogenic cell (mixed lymphocyte response) challenge was assessed. At the same time, peripheral blood lymphocytes and thymocytes were collected and prepared for flow cytometry analysis. Proliferative responses to both T cell mitogens and allogeneic splenocytes were significantly increased (P less than 0.05) by rcGH treatment, while the combined T4-rcGH treatment resulted in a significant increase in allogeneic and in concanavalin A responsiveness, but not in the response to phytohemagglutinin. All supplemented groups showed a significant decrease in the mean fluorescent intensity for CT-1a+ thymocytes, while thymocytes from birds receiving either T4 or rcGH alone had higher proportions of CD4+ and CD8+ cells. The monoclonal antibody staining of thymocytes from T4-rcGH-supplemented animals more closely resembled that of the unsupplemented controls. Among the peripheral blood lymphocytes, there were no changes in the numbers of CD4+, CD8+, or sIg+ cells as a result of treatment. The mean fluorescent intensity of sIg+ cells was significantly decreased, however, as a result of T4 supplementation when given either alone or in combination with rcGH. Finally, the mean fluorescent intensity ratios of CD4+ to CD8+ cells was significantly increased as a result of rcGH supplementation. These results strongly support a role for both the thyroid hormones and growth hormone in regulating and/or enhancing immune function, with changes in functional responses paralleled by concomitant changes in the T cell populations as expressed by shifts in T cell surface marker expression.

Animals

Circannual changes in immune function.

Adrenocortical activity varies on a circannual basis with increased secretion in the winter and decreased secretion in the summer. One consequence of this variation is a circannual pattern in immune function. Adrenal corticosteroids, especially glucocorticoids, depress cellular immune function and seem to be more effective against T-suppressor cells. Thus, when adrenocortical activity is elevated, T-cell activity is depressed and B-cell activity is elevated. To the extent that T-cell "surveillance" is depressed in winter, there should be increased lymphoproliferative cancer risk during winter and in regions characterized by cold climates. This article presents data which suggest: (1) a winter, adrenal-corticoid induced, depression of T-cell function which is accompanied by elevated B-cell function; (2) elevated serum immunoglobulin levels in the winter; and (3) an inverse relationship between ambient temperature and serum immunoglobulin levels. The circannual pattern in immune function could help explain increased lymphoproliferative cancer risk, as a side effect of immunosuppression therapy during organ transplants, and as a function of latitude.

Adrenal Cortex Hormones

Stress, emotion, and human immune function.

This article provides a review of empirical evidence linking emotional processes to immune function in humans. Acute stressors have produced mixed effects on immunity, presumably through differential activation of physiological stress systems. Chronic stress has been associated with suppression of immune function, and there is evidence that the immune system may not adapt over time. Effects of stress accompanying social disruption and psychological depression, when demonstrated, have been consistently adverse. Certain personality styles may enhance or degrade immune response. Relationships between psychosocial factors and immunity have been identified for several diseases, including cancer, acquired immune deficiency syndrome, and autoimmune diseases; psychosocial interventions have been tested with variable results. Theoretical and methodological considerations are summarized and directions for future research suggested.

Acquired Immunodeficiency Syndrome

Hepatic inflammation, hepatitis B replication, and cellular immune function in homosexual males with chronic hepatitis B and antibody to human immunodeficiency virus.

We measured serum aspartate transaminase (AST) concentration and serum hepatitis B virus (HBV) DNA concentration in homosexual men with chronic HBV infection and a spectrum of immune deficiency as a result of exposure to human immunodeficiency virus (HIV). Serum AST and HBV DNA concentrations were similar in patients with varying immune function as indicated by in vivo criteria (diagnosis and skin tests reactivity) and in vitro criteria (lymphocyte transformation responses to mitogens and Candida and tetanus antigens) and were unrelated to the number of circulating T cells, suppressor/cytotoxic cells, helper cells, natural killer cells, and the helper:suppressor ratio. Serum AST concentration and indices of cellular immune function were similar in patients with varying HBV replicative activity (high and low HBV DNA concentrations). The observed lack of relationship between serum AST concentration and indices of cellular immune function and HBV replication suggests either that other factors determine the severity of hepatic inflammation in chronic HBV infection, or that currently available tests of cellular immune function and HBV replicative activity do not accurately reflect processes in the liver.

Adult

Immune function among normal Guamanians of different age.

To determine if immune function differed in normal Guamanian Chamorros at various ages we measured the percentage and total numbers of lymphocytes and T-lymphocytes, their response to phytohemagglutinin (PHA), and serum levels of immunoglobulin A, G, and M in subjects 20 to 83 years of age. Regression analysis showed highly significant negative correlations for total lymphocytes and T-cells with age and a less significant negative correlation for PHA response with age in this population. Serum IgA levels increased with age, IgM levels declined, and IgG levels were unchanged. These findings are similar to, but less marked than, immunologic aberrations previously observed in Guamanians with amyotrophic lateral sclerosis or Parkinsonism-dementia. The occurrence of prominent differences in immune functions between younger and older individuals in a population where neurofibrillary degeneration in brain occurs at an early age and neurodegenerative and other age-related diseases are highly prevalent suggests the possibility that immunity and age-associated degenerative disease may be linked etiologically in this population.

Aged

Dietary fat, plasma lipoproteins, and immune function in middle-aged American men.

Dietary fat has been incriminated as a positive risk factor for the development of neoplasia in human populations. We used adipose tissue fatty acid analysis as an index of dietary fat intake to study the association between dietary fat and immune function in a group of 94 free-living American males (avg age 47 years). Immunocompetence was tested by a battery of T- and B-lymphocyte stimulation tests and also by natural killer (NK) cell activity. Correlations were sought between fatty acid composition, plasma lipids, and immune responsivity. The degree of unsaturation of the diet over a polysaturated-to-saturated fat ratio range of 0.54-1.01 had no predictable effect on the immune function. Stepwise regression analysis showed that the concentrations of plasma triglycerides and cholesterol and its subfractions did not explain any of the variance in the immune tests. Palmitic acid (16:0) was associated with 7% of the variance of the response to C. albicans and E. coli, perhaps through influencing B-cell activity. Stearic acid (18:0) was correlated negatively to concanavalin A responsivity (18% of the variance) and positively to NK activity (20% of the variance). If impaired in vitro immune function is a marker of increased risk for carcinogenesis, then our data do not support a role for dietary fat influencing in any systematic manner lymphocyte function in vitro, as reflected by proliferative response or NK activity. Further, plasma lipoproteins, in particular cholesterol levels, did not appear to affect any immune function test. It remains to be studied whether dietary fat, lipoproteins, or fat-soluble substances may influence membrane structure and function and prostaglandin formation as alternative pathways in the promotion of neoplasia.

Adipose Tissue

Prognostic significance of immune function parameters in patients with chronic lymphocytic leukaemia.

We determined immune function parameters in 41 newly diagnosed patients with chronic lymphocytic leukaemia (CLL) and correlated these findings with the clinical data and the subsequent course of the disease. The ratio of helper to suppressor T cells (CD4/CD8), the proportion of circulating natural killer (NK) cells and the NK activity were significantly low in clinical stage B and C patients. Among patients presenting with advanced disease, those who subsequently had a more severe course, characterised mainly by frequent respiratory infections, were found to have at presentation a significantly lower CD4/CD8 ratio (x +/- SEM = 0.95 +/- 0.09, vs 1.28 +/- 0.14), a very low proportion of NK cells (4.78 +/- 0.85, vs 11.75 +/- 2.1%) and decreased amount of gamma-globulins (0.66 +/- 0.08, vs 0.97 +/- 0.09 g/dl), in comparison with patients with a much milder later course. These simple parameters of immune function seem to have prognostic value for patients with CLL.

Antigens, CD

Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: relation to duration of treatment.

Recently, abnormalities of cell-mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia-A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T-helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T-suppressor cells, Con A-activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.

Acquired Immunodeficiency Syndrome

[Preliminary study on the immune function of red cells in patients with pregnancy-induced hypertension].

This study compared the immune adherent function of red cells, circulating immune complex (CIC) and T lymphocyte immune function in cases of pregnancy induced hypertension (30 cases) and normal pregnancy (30 cases). In the former group the rosette rate of red cells C3b receptor was 8.8 +/- 3.2% (normal rate: 19.4 +/- 6.0%), and rosette rate of E-RFC was 46 +/- 2 +/- 7.3% (normal rate: 62.3 +/- 6.4%). In women with normal pregnancy, the former was 16.9 +/- 4.8%, and the latter was 58.0 +/- 8.3%. In women with pregnancy induced hypertension, the immune adherent function of red cells and T lymphocyte immune function were both lower than those in normal pregnant women, while CIC was higher. In normal pregnant women, the immune adherent function of red cells and T lymphocyte immune function were lower than those in the non-pregnant, while CIC was higher. The mechanism and significance of the red cells immunological adherent function in pregnancy induced hypertension were discussed.

Antigen-Antibody Complex

Immune function during intravenous administration of a soybean oil emulsion.

The effect of a continuous infusion of a soybean oil emulsion on immune function was evaluated in 40 malnourished patients who were randomized to receive preoperatively either a 25% glucose-5% amino acid solution (group G) or a 15% glucose-3.3% Intralipid-5% amino acid solution (group G-F). Average length of total parenteral nutrition (TPN) was 10.3 +/- 0.9 days for group G and 9.0 +/- 0.8 days for group G-F. Initial nutritional status and response to TPN were similar for both groups. Immune function was assessed before TPN and after nutritional repletion prior to surgery for each patient. The levels of immunoglobulins, C3, C4, circulating B lymphocytes and T lymphocytes, suppressor T lymphocytes, natural killer cell activity, and monocytes were normal before TPN and after nutritional therapy. However, the total number of T cells and helper T cells were low before TPN and remained so after TPN. In addition, lymphocyte function measured by the lymphocyte blastogenic response to phytohemagglutinin and pokeweed mitogen was depressed prior to TPN and was not improved by either regimen. Neutrophil chemotaxis and bactericidal activity were not affected by either nutritional regimen while neutrophil phagocytosis was enhanced before TPN and remained elevated throughout TPN with either regimen. There were no differences in infection rates during TPN. The addition of Intralipid to the TPN regimen did not alter immune function in these patients who showed depressed cell-mediated immunity before TPN compared with the standard glucose TPN regimen.

B-Lymphocytes