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Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males.

OBJECTIVES: To determine: a) whether the cell-mediated immune response during sepsis differs in females vs. males; and b) whether the survival rate in females is different than in males after a septic insult. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and proestrus female mice underwent cecal ligation puncture to induce sepsis. The mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and IL-3 release, was determined by bioassay. In additional studies, survival rate after septic challenge was measured over 10 days. Splenocyte proliferative capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male, but not in female, septic mice. Furthermore, the survival rate of septic female proestrus mice was significantly higher than in comparable male mice. CONCLUSIONS: These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.

Adolescent↗

Effect of in vivo infusion of granulocyte colony-stimulating factor on immune function.

As the applications of hematopoietic growth factors increase, their complex impact on host defense and immune responses continues to unfold. The effect of the administration of granulocyte colony-stimulating factor (G-CSF) on bacterial defense, proliferation of lymphocytes, and cytokine production by lymphocytes and peripheral blood mononuclear cells (PBMC) was studied. The effect of G-CSF administration on the phenotype of the cells in the major hematopoietic organs was studied as well. ACI rats were given 10 mg/kg/day G-CSF or vehicle daily for 4 days. Isolated bone marrow neutrophils and enterocytes from treated animals showed a greater bactericidal activity than controls. Proliferation of mitogen-stimulated lymphocytes and PBMC was reduced in G-CSF-treated animals. The production of proinflammatory cytokines, tumor necrosis factor (TNF), and interleukin 6 (IL-6) by lymphocytes and PBMC was reduced by G-CSF pretreatment. G-CSF administration caused an increase in IL-4 (Th2 cytokine) release and a decrease in interferon-gamma (IFNgamma, Th1 cytokine) release by mitogen-stimulated lymphocytes. Cytometric analysis of cells in the progenitor cell region indicated a large increase in immature cells in the bone marrow of G-CSF-treated animals compared with sham along with an increase in B cells and a decrease in polymorphonuclear leukocytes (PMNs). In addition, cytometric analysis showed a large increase in PMNs in blood and splenocytes of the treated animals compared with sham. This study confirms and extends previous observations that G-CSF administration has a number of effects that might simultaneously enhance host defense while reducing the risk of developing uncontrolled systemic inflammation. This may also be efficacious in prolonging graft survival and reducing graft vs. host disease.

Animals↗

Vitamin B6 and immune function in the elderly and HIV-seropositive subjects.

Vitamin B6 plays an important role in immune response. A recent investigation of healthy elderly subjects in a vitamin B6 depletion-repletion study indicates that B6 deficiency impairs interleukin-2 production and lymphocyte proliferation. Another study in HIV-1-infected patients found impaired immune responsiveness in patients with compromised vitamin B6 status.

Aged↗

Immune function and lifestyle of taxi drivers in Japan.

Many studies have reported that stress affects the immune system. It is known that professional drivers are exposed to various forms of job-related stress. The aim of the present study was to investigate the job stress of taxi drivers based on the mitogen responses and cytokine production of peripheral blood lymphocytes (PBMC), combined with interviews on lifestyles and income. We examined randomly selected male taxi drivers aged 40-59 years who were members of the Kansai District Union of Private Railway, Hire, and Taxi at the end of 1992 and 1993. At the end of 1993, they were struck by a severe economic depression. The lymphocyte proliferative responses to phytohemagglutinin (PHA), concanavalin A (ConA), poke weed mitogen (PWM), and PHA-induced interleukin-2 (IL-2) and IL-4 production of the taxi drivers were at the same level as those of the control subjects as measured in 1992. The mitogen responses and IL-2 production of taxi drivers were found to have significantly decreased in 1993, while their IL-4 production was significantly elevated. Lifestyles of normal PHA respondents were significantly different from those of low-PHA respondents in 1992. However, in 1993, these differences were unclear. The immune alterations of taxi drivers who were prohibited from working overtime were more profound than those of the drivers who were allowed to do so. These results indicate that in addition to driving stress, the daily earnings affect taxi drivers as a strong stress or that induces immunological changes.

Adult↗

The effect of methionine and aflatoxin on immune function in weanling pigs.

To investigate the effect of aflatoxin (AF) and dietary methionine (MET) on immune responses of swine, a total of 288 pigs weaned at 21 d of age were allotted to 12 dietary treatments arranged in a 3 x 4 factorial arrangement in a randomized complete block design. Diets consisted of a corn-soybean meal diet (.95% lysine, .30% MET, and .32% cystine) containing either 0, 140, or 280 ppb of AF and supplemented with either 0, .15, .30, or .45% DL-MET. Immune response measurements were made after the pigs had received their diet for 3 wk. Antibody response to sheep red blood cells (SRBC) was measured 0, 7, and 14 d after i.m. injection of 2.5 mL of a 20% SRBC suspension. Total serum immunoglobulin (Ig) M and IgG were measured using an ELISA. In vivo cellular immunity was measured using a phytohemagglutinin (PHA) skin test. Skin thickness was measured 0, 6, 12, 24, and 36 h after s.c. injection of .1 mL of PHA (1.50 mg/mL). In vitro cellular immunity was measured using a lymphocyte blastogenesis assay. Antibody response to SRBC and serum IgM and IgG concentrations were not affected by dietary treatments. Skin thickness response at 6 h after injection was maximal when .45% MET was added to diets containing 280 ppb of AF, whereas the response was maximal at .30% supplemental MET for the 0 and 140 ppb of AF diets (AF x MET interaction, P < .10). Skin thickness was reduced linearly (P < .10) with increasing dietary AF at 12 and 24 h after PHA injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗

Tumor growth and immune function in mice during hind-limb unloading.

INTRODUCTION: Spaceflight is associated with changes in several immune parameters. Studies in rodents and humans have shown a decrease in resistance to bacterial and viral infections. However, the effect of spaceflight conditions on tumor immunity has not been explored. METHODS: The hindlimb unloading (HU) murine model of spaceflight was used to assess growth and immune reactivity to the S1 509a tumor cell line during HU as a model of microgravity. Changes in splenic mass of mice in the HU model were compared with mice in orthostatic suspension and standard housing controls. Furthermore, the role of host immunity in these changes was confirmed using mice with the severe combined immunodeficiency (SCID) mutation. RESULTS: Mice in the HU model demonstrated significantly increased tumor growth (p < 0.01), greater splenic atrophy, and a significantly diminished delayed-type hypersensitivity response to tumor antigens (p < 0.05) compared with controls. However, when immunodeficient mice were employed, no difference in tumor growth was observed. DISCUSSION: Our findings suggest antitumor immunity is inhibited in antiorthostatic suspension. The lack of a difference in mean tumor size in SCID mice in antiorthostatic suspension compared with standard housing controls supports the concept that HU alters host immunity against the S1 509a tumor. Further studies are warrranted to delineate the precise effects of spaceflight on host immunity, carcinogenesis, and tumor progression.

Animals↗

[Observation of immune function in 115 elderly patients with pulmonary tuberculosis].

This paper tested the indexes of the cellular immunity and the humoral immunity of initially treated 115 old patients with pulmonary tuberculosis, and the data were compared with these values of healthy elder and youth and middle aged patients with pulmonary tuberculosis. The results showed that the indexes of the cellular immunity elderly patients with pulmonary tuberculosis decreased (LTT Et-RFC Ea-RFC the discrepancy significantly, P less than 0.05), and the index of the humoral immunity increased (the varying of all the indexes P less than 0.01) compared with the health elders. All the immune indexes of the old pulmonary tuberculosis had no significant difference except for IgA compared with youth and middle aged patients.

Aged↗

[Effect of thyroid immune liquor on erythrocyte immune function in patients with autoimmune thyroiditis].

Thirty cases of autoimmune thyroiditis (AT) were treated with thyroid immune liquor (TIL). The results showed that the activity of erythrocyte C3b receptor and erythrocyte immune adherence enhancing factor were significantly increased, while erythrocyte immune complex and erythrocyte immune adherence inhibiting factor were decreased. The thyroid microsome-antibody and thyroid globulin-antibody were also significantly decreased. This indicates that the TIL has adjustive effect on humoral immunity and cellular immunity in patients with AT.

Adjuvants, Immunologic↗

[Effect of Shenqi Fuzheng injection (SFI) on immune function in patients with congestive heart failure].

OBJECTIVE: To study the effect of Shenqi Fuzheng injection on the humoral immunity (IgG IgM IgA), cellular immunity (T-lymphocyte subsets), Superoxide dismutase (SOD). Lpo and Plasma viscosity in the patients with congestive heart failure (CHF). METHODS: Sixty patients with CHF, whose heart function belonged to NYHA grade II-IV were randomly divide into two groups. The treaded group were treated with SFI 100 ml, and the control group were treated by nitroglycerine in jection 10 mg, the drug were administered respectively by adding in 5% glucose solution 500 ml for intravenous dripping, once a day, 20 days as one therapeutic course. Venous blood from cubital vein was collected before and after treatment to detect the IgG, IgM, IgA, T-lymphocyte subsets, SOD, LPO and Plasma viscosity. RESULTS: The clinical heart function markedly improved rate and total effective rate in the treated group was singificantly better than those in the control group respectively (P < 0.05). the left ventricular ejecting frection (LVEF) and end syctolic volume (ESV) were improved in both group (P < 0.05, P < 0.01), and the improvement in the treated group was superior to that in the control group (P < 0.05). In the treated group after treatment, the CD4, SOD level and CD4/DC8 ratio increased (P < 0.05), level of LPO, IgG and IgM lowered (P < 0.05) significantly, while those in the control group were not changed singificantly (P > 0.05). Plasma viscosity of treatment group also got better improved than before (P < 0.05), and there was a significantly difference between the two groups after treatment (P < 0.05). CONCLUSION: SFI Can improve the immune funtion of CHF patients, and can be taken as an importmant auxiliary treatment for CHF.

Adjuvants, Immunologic↗

Peripheral human T lymphocyte maintenance of immune functional capacity and phenotypic characteristics following in vivo cocaine exposure.

The effects of cocaine exposure upon the host's immune response is equivocal since a variety of studies have generated conflicting conclusions, often as the result of differences between in vitro and/or animal models and the actual conditions experienced in humans who are acutely abusing this drug. To further address this issue, we have studied a group of patients who were positive for cocaine or cocaine metabolites and we evaluated a variety of functional parameters of T-lymphocytes and other peripheral lymphoid cell populations, as well as immunophenotypic characteristics of these cells. When compared to normal controls and patients who were negative for cocaine, we found that the cocaine-positive patients had T-cell functional assays which were essentially normal, with the exception of a slight depression in PHA stimulation. Likewise, the immunophenotype of the peripheral blood lymphocytic populations showed normal percentages and numbers of their T cell subsets (CD4, CD8), NK cells, and B cells. Multicolor flow cytometry analysis revealed no difference in T cell subpopulations positive for the "memory" marker, CD62L. No correlation could be established between levels of cocaine or cocaine metabolites and any phenotypic, demographic, or functional parameter. In summary, these results demonstrate that individuals acutely exposed to cocaine do not show markedly altered T cell function or fluctuations in phenotypically identified cell populations. These studies imply that acute cocaine exposure does not predispose individuals to grossly apparent immunosuppression. However, the possibility that subtle, transient, or more specific changes in the immune system may be incurred by use of cocaine, particularly with chronic exposure, remains to be determined.

Adult↗

[The characteristic changes of immune function with aging].

It is well-known that the most prominent age-related immunological abnormalities were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigens. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample. The sixth, the combined stimulation with PMA and ionomycin could induce proliferative response to highly purified T cells, T cell subsets and B cells. The degree of age-related decline of the proliferative response of CD-8 positive T cells was most significant, that of CD-4 positive ones was next and that of B cells was least. The seventh, although the maximum of c-myc mRNA level was attained at 2 hr after the stimulation and similar amount between the both age groups, the amount of mRNA at 8 or 24 hr was rather higher in the aged T cells than in the young ones. The reduction of the degradation rate of c-myc mRNA seemed to be the cause. We found no difference of the maximum amount and kinetics of c-myb mRNA between both age groups in T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Effect of the antiviral compound MDL 20,610 on some aspects of murine immune function.

At physiologically relevant concentrations an antiviral compound should not perturb the host's ability to mount an immune response against the infecting virus or some other opportunistic pathogen. The purpose of this study was to evaluate the immunomodulatory activity of the antiviral compound MDL 20,610 using murine models. When tested in vitro at the limit of aqueous solubility (6 microM), MDL 20,610 has no significant effect on neutrophil function as assessed by cell migration against FMLP and LTB4 gradients, myeloperoxidase secretion or 0.-2 production. In addition, 6 microM MDL 20,610 has no significant effect on macrophage function as determined by 0.-2 production, Ia and Mac-1 antigen expression and expression of Fc gamma receptors. Finally, MDL 20,610 does not significantly affect in vivo (1-100 mg/kg/day) NK cell activity or DTH to oxazolone; but treatment of mice with 50 or 100 mg MDL 20,610/kg/day significantly (P less than 0.01) enhances SRBC IgM antibody synthesis. These data indicate that MDL 20,610 is relatively devoid of immunomodulatory activity.

Adjuvants, Immunologic↗

Evaluation of immune function in mice exposed to Ordram.

The potential effects that the thiocarbamate herbicide Ordram has on the immune system of mice was evaluated following 12 days of acute dosing by oral gavage. Dosages of Ordram ranging from 20 to 320 mg/kg/day had no consistent significant effects on a variety of immune parameters investigated. The immune parameters measured were the following: body and lymphoid organ weights; splenic natural killer (NK) cell activity; lymphoproliferative responses to B and T lymphocyte mitogens and allogeneic spleen cells in a one-way mixed lymphocyte reaction; and delayed-type hypersensitivity and antibody responses to sheep red blood cells (SRBC). The effects that the immunosuppressant cyclophosphamide has on these immune parameters was also examined. The results indicate that Ordram does not appear to affect key parameters of the immune system of mice under the conditions of exposure employed.

Administration, Oral↗

Effects of a long-term training program of increasing intensity on the immune function of indoor Olympic cyclists.

We have studied, on blood samples, the level of immunocompetence (concentration of immune cells, phagocytic process of polymorphonuclear neutrophils, proliferative response of lymphocytes to mitogens), the ascorbic acid content of such immunocompetent cells and the "stress hormone" status (cortisol, ACTH and beta-endorphin) of 10 cyclists, members of the Spanish Indoor Olympic Team and participants in the Olympic Games of Barcelona '92. The study was performed twice during their training for such an event: during the third year of the program (February, 1991) and immediately before the Games (June, 1992). As regards the phagocytic process of neutrophils, we studied the different steps of this process: adherence to endothelium, directed mobility or chemotaxis, ingestion of latex beads and superoxide anion production measured by the nitroblue tetrazolium (NBT) reduction test. We observed a statistically significant increase in chemotaxis and NBT reduction activity just before the Games as compared to the third year of the program, whereas variations were not found in the other parameters. The values of the proliferative capacity of lymphocytes were slightly higher in June '92 than in February '91, but no statistically significant differences were found. The ascorbic acid content decreased strikingly (especially in lymphocytes) immediately before the Games. Regarding the stress hormones and neuropeptides (cortisol, ACTH and beta-endorphin), we observed an increase in serum ACTH and beta-endorphin levels in the last determination (June '92) in comparison to the first one (February '91). These results suggest that, at the end of a long-term training program. no immunosuppression occurs, although an important increase in the concentration of stress hormones (ACTH and beta-endorphin) is found. This is probably caused by the psychological stress associated to the participation in such an important event as the Olympic Games.

Adrenocorticotropic Hormone↗

Systems biology in systemic lupus erythematosus: integrating genes, biology and immune function.

Overactive B cells, abnormally activated T cells and inappropriate handling of cellular debris by the innate immune system are central in the pathogenesis of systemic lupus erythematosus (SLE). Genetic studies in SLE patients have unraveled allelic variations in genes encoding key molecules that control inter- and intra-cellular signaling and play a role in the abnormal handling of apoptotic material. Despite recent breakthroughs though, it is still unclear how exactly genes and environment interact to produce the characteristic immune dysregulation in SLE.

Animals↗

Effect of a low beta-carotene diet on the immune functions of adult women.

We examined the effect of beta-carotene depletion and repletion on the immune status of nine healthy women who lived in the metabolic suite for 100 d. For the first 4 d all women were fed a basal diet supplemented with 1.5 mg beta-carotene/d (baseline). During the next 68 d, the basal diet without beta-carotene supplementation was fed to all subjects (depletion), and during the last 28 d the diet of each women was supplemented with 15.0 mg beta-carotene/d (repletion). Neither beta-carotene depletion nor repletion significantly (P < or = 0.05) altered proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, in vitro production of soluble interleukin 2 receptor, or the concentration of circulating lymphocytes and their subsets. Thus, in healthy adults consuming adequate vitamin A, beta-carotene depletion had no adverse effect on the indexes tested, nor was there any beneficial effect of modest beta-carotene supplementation.

Adolescent↗

Nutrition in pediatric HIV infection: setting the research agenda. Nutrition and immune function: overview.

Malnutrition can have adverse, even devastating effects on the antigen-specific arms of the immune system and on generalized host defensive mechanisms. Protein/energy malnutrition and/or deficiencies of single nutrients that assist in nucleic acid metabolism generally lead to atrophy of lymphoid tissues and dysfunctions of cell-mediated immunity. Deficiencies of single nutrients can impair production of key proteins. Trace element deficiencies are often multifactorial. Essential fatty acid deficiencies can reduce or perturb the synthesis of cytokine-induced eicosanoids. Arginine deficiency can diminish the production of nitric oxide, and deficiencies of antioxidant nutrients can allow increases in the damaging effects of free oxygen radicals. Humoral immunity continues to be maintained, although new primary responses to T-cell-dependent antigens are generally subnormal in both magnitude and quality. Immunological dysfunctions associated with malnutrition have been termed Nutritionally Acquired Immune Deficiency Syndromes (NAIDS). Infants and small children are at great risk because they possess only immature, inexperienced immune systems and very small protein reserves. The combination of NAIDS and common childhood infections is the leading cause of human mortality. NAIDS can generally be corrected by appropriate nutritional rehabilitation, but from a viewpoint highly important to this Workshop, AIDS and NAIDS are intensely synergistic. AIDS-induced malnutrition can lead to the secondary development of NAIDS, with its much broader array of additional immunological dysfunctions. The complex and far reaching insults to the immune system caused by NAIDS, and the synergistic combination of NAIDS and AIDS, thereby hasten the demise of many victims of AIDS. Aggressive nutritional support for children with HIV infections could delay, or lessen, the development of NAIDS and avoidance of NAIDS would improve both quality and length of life.

Acquired Immunodeficiency Syndrome↗

Immune function at diagnosis in relation to responses to therapy in acute lymphocytic leukemia of childhood.

Tests of immune capacity were performed on blood from 49 children with newly diagnosed, untreated acute lymphocytic leukemia, and relation to prognosis was determined. Patients were treated with multiple-drug therapy and prophylactic cranial irradiation. Median follow-up time was 16 mo (range 10--37 mo). Principal unfavorable findings at diagnosis were absolute numbers of T lymphoid cells outside the range 850--2500/mul blood, absence of whole blood responses to phytohemagglutinin in vitro, a low titer of complexed antibody, and the presence in serum of free leukemic blast cell membrane antigen. Fourteen patients showed two or more unfavorable findings at diagnosis. Eleven of these have died. Four of the remaining 35 patients have died. A shorter duration of first remission was found among patients with abnormal numbers of T cells at diagnosis. The findings suggest that the immunologic capacity of the patient at diagnosis is an important determinant in responses to therapy.

Adolescent↗