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Prolactin modulates survival and cellular immune functions in septic mice.

BACKGROUND: The immunomodulatory properties of the pituitary hormone prolactin have been demonstrated. It was proposed that prolactin is important in maintaining normal immune response in several pathological states. We investigated the effect of prolactin administration on the survival and cellular immune functions during systemic inflammation. MATERIALS AND METHODS: Male NMRI mice were subjected to laparotomy (LAP) or sepsis induced by cecal ligation and puncture (CLP). Mice were treated with either saline (LAP/saline; CLP/saline) or prolactin (LAP/PRL, CLP/RPL; 4 mg/kg s.c.). Survival of septic mice was determined 24 and 48 h after CLP. Forty-eight hours after the septic challenge, the proliferative capacity, cytokine release (IL-2, IL-6, IFN-gamma) and apoptosis of splenocytes were determined. Additionally, monitoring of circulating leukocyte distribution was performed (WBC; CD3+, CD4+, CD8+, B220+, NK1.1+, F4/80+ cells by FASCan). RESULTS: CLP was accompanied by a mortality of 47% and induced a decrease in splenocyte proliferation and apoptosis rate. Administration of prolactin significantly increased the mortality of septic mice (81%). This was paralleled by a further decrease of splenocyte proliferation and an increased splenocyte apoptosis. In addition, administration of prolactin augmented the sepsis-induced inhibition of IL-2 release, attenuated the sepsis-induced inhibition of IFN-gamma release, and did not affect the release of IL-6. However, prolactin did not affect the sepsis-induced changes of circulating leukocyte subpopulations. CONCLUSIONS: We conclude that prolactin has profound immunomodulatory properties and that administration of prolactin in pharmacological doses is associated with a decreased survival and an inhibition of cellular immune functions in septic mice.

Animals↗

[Effect of Chinese drugs mixture on immune function of patients with extremely severe burn].

OBJECTIVE: To study the regulatory effect of Qinghuo Baidu Yin (QHBDY, a mixture prepared with Chinese drugs) on immune function of patients with extremely severe burn (ESB). METHODS: Thirty patients with ESB were divided into two groups, conventional therapy was given to both groups, but QHBDY was given to the treated group additionally. Immunological indices, including peripheral blood T-lymphocyte subsets, immunoglobin (IgG, IgA and IgM) and complement (C3 and C4) were determined 3 weeks after treatment to evaluate and compare the therapeutical effect in the two groups. RESULTS: Compared with the control group, CD3, CD4, CD4/CD8, immunoglobin (IgG, IgA and IgM) and complement (C3 and C4) levels were markedly decreased in degree, and recovered earlier and quicker, with CD8 increased mildly (P < 0.01) and turned back more quickly. And so did the parameters of the treated group in comparing with that of the control group at anytime (P < 0.05 or P < 0.01). CONCLUSION: Chinese drugs mixture shows the regulatory effect on both cellular and humoral immune function in patients with ESB.

Adjuvants, Immunologic↗

Alterations in cell-mediated immune functions induced in mouse splenic lymphocytes by polycyclic aromatic hydrocarbons.

The effects of varying doses of three polycyclic aromatic hydrocarbons, 3-methylcholanthrene (MCA), benzo(a)pyrene (BaP), and benzo(e)pyrene (BeP), on cell-mediated immune functions of in vivo mitogen-activated splenic lymphocytes were measured. Inbred mice (C57, C3H, and DBA) were given injections i.p. with phytohemagglutinin to activate splenic lymphocytes and were subsequently treated, via the same route, with polycyclic aromatic hydrocarbon compounds. Isolated and T-cell-enriched mononuclear cell populations were assayed for aryl hydrocarbon hydroxylase activity, blastogenesis, antigen-specific cell-mediated cytotoxicity, and the percentage of macrophages. Under optimal conditions of phytohemagglutinin injection (1000 micrograms/20-g mouse) for 96 hr and MCA treatment (50 mg/kg of body weight) for 24 hr prior to sacrifice, aryl hydrocarbon hydroxylase was induced 5-fold. Tumorigenic doses of MCA (10 to 50 mg/kg of body weight) suppressed blastogenesis 40 to 60% in C57 and C3H lymphocytes but had no effect on DBA splenic lymphocytes. BaP and BeP had little or no effect on blastogenesis. MCA and BaP were clearly separated from BeP in the suppression of cell-mediated cytotoxicity. MCA and BaP suppressed cell-mediated cytotoxicity 40 to 80% in T-cells from all three strains, while BeP had no effect. MCA reduced the percentage of macrophages in a dose-dependent fashion compared to a stimulatory action by BaP and BeP. These results suggest that mitogen-activated and aryl hydrocarbon hydroxylase-induced splenic lymphocytes metabolize MCA and BaP to immunocytotoxic metabolites. A suppression of monocyte-macrophage function would account for the inhibition of blastogenesis. These early alterations in cell-mediated immune functions produced by tumorigenic doses of MCA and BaP may result in defective immunosurveillance mechanisms and enhance the development of polycyclic aromatic hydrocarbon-induced tumors in responsive mice.

Animals↗

[Influence of dietary selenium level on immune function of rats with esophageal tumors induced by methylbenzylnitrosamine (NMBzA)].

The influence of dietary selenium of the incidence of esophageal tumor induced by NMBzA and the immune function during carcinogenesis were studied in rats fed with Torula yeast diet and survived for 18 weeks. The incidences of esophageal tumors were statistically not significant among rats on normal, high and low selenium intake (P greater than 0.05). The level of plaque forming cells (PFC), delayed type hypersensitivity (DTH), natural killer cell activity (NK) were significantly higher in the high selenium diet group than those of the low selenium diet group (P less than 0.05). The authors believe that the modulation of dietary selenium can alter the immune function of animals during carcinogenesis but the anticarcinogenic effect of selenium still needs further study.

Animals↗

Immune function in marathon runners.

Quantitative immunoglobulins (IgG, IgA, IgM) and leukocyte phagocytosis and killing were studied in 20 male marathon runners to determine if rigorous physical conditioning affects immune function. C3, C4, Properdin Factor B, T and B cells, and phytohemagglutinin and pokeweed mitogen stimulation of lymphocytes were determined in selected runners. Complete blood counts, including platelets, were obtained for the group. Mean immunoglobulin values for IgG, IgA and IgM were within normal limits. Ten runners (50%) had slightly low total lymphocyte counts (less than 1500/mm3). Leukocyte phagocytosis and killing was consistently normal. Nine marathoners felt that running had increased, and one felt that it had decreased their resistance to respiratory infections. This could not, however, be correlated with significant changes in immune parameters. We conclude that long distance running has no effect on immune function.

Adult↗

Effect of midbrain stimulus-induced analgesia on immune function in humans.

Electrical stimulation of midbrain structures produces significant and clinically useful analgesia in humans. However, it has been suggested to have immunosuppressive effects in animals. We evaluated immune function in two women who were utilizing implanted midbrain electrodes for pain control. An elevated B cell percentage was observed in one patient after a 72-h control rest period and this was followed by a reproducible fall in B cells after acute stimulation. However, midbrain electrical stimulation did not appear to have any other acute or chronic effects on these persons' immune functions.

Analgesia↗

Impact of feeding regimen on behavioral and physiological indicators for feeding motivation and satiety, immune function, and performance of gestating sows.

The effect of daily or interval (every 3 d) feeding on body weight change, blood glucose and cholecystokinin (CCK) concentrations, immune function, and behavioral activity were determined during the gestation period of sows. Sows were fed a corn-soybean meal diet either 2 kg daily or 6 kg once every 3rd d (interval). Body weight changes for the 42-d trial period were not different (P > .05) between regimens. Blood glucose concentrations were similar before feeding (P > .05). Two hours after feeding, glucose concentrations increased in interval-fed sows but not in daily-fed sows (P < .05). Premeal plasma CCK concentrations were greater for daily-fed sows than for interval-fed sows (P < .05). The CCK concentrations in sows of both regimens increased after feeding above premeal levels (P < .05), and interval-fed sows exhibited higher concentrations than daily-fed sows (P < .05). Immune function as evaluated through mitogen-induced proliferation of T cells was greater in daily-fed sows than in interval-fed sows (P < .05). Daily-fed sows were more active overall and on any given day than interval-fed sows (P < .05) and thus seemed to expend more energy. Further, daily-fed sows exhibited higher levels of mouth-based activities (i.e., sham chewing, licking, appetitive and consummatory feeding behavior, and excess drinking) than sows restricted to consumption of one large meal every 3rd d. These indicators suggest that feeding motivation significantly affected overall performance of sows. This study emphasizes the need for evaluating the impact of feeding regimens and meal size on feeding motivation and, ultimately, on the well-being of the gestating sows.

Animals↗

Effects of propofol and taurine on intracellular free amino acid profiles and immune function markers in neutrophils in vitro.

We have examined the effects of propofol, taurine, and the combination of propofol and taurine on amino acid profiles and the immune function markers superoxide anion (O2-), hydrogen peroxide (H2O2), and released myeloperoxidase (MPO) activity in neutrophils (PMN). Propofol led to significant changes in the dynamic PMN-free amino acid pool. Exogenous taurine significantly reduced PMN neutral amino acid and alpha-aminobutyrate (alpha-aba) as intracellular taurine increased. Incubation with propofol plus taurine resulted in lower intracellular taurine levels and elevated alpha-aba and neutral amino acid concentrations compared to propofol alone. Concerning PMN immune function markers, propofol significantly decreased O2- and H2O2 formation and released MPO. Taurine led to an increased release of MPO and concomitant significantly reduced O2- and H2O2 levels. When propofol and taurine were applied together they appeared to act additively with regard to superoxide and hydrogen peroxide formation. In the case of MPO, taurine neutralized propofol's effects, supporting the idea that MPO activity may be regulated by taurine. We believe therefore that taurine is important for strengthening PMN host defense capability, although the mechanisms are not yet clear. Moreover, taurine appears to act primarily by altering the PMN osmotic balance, while propofol seems to affect PMN amino acid metabolism and/or uptake and release.

Adult↗

[Quality of tuberous root of Liriope spicata (Thunb.) Lour. var. prolifera Y.T.Ma and Ophiopogon japonicus (L.F.) Ker-Gawl.--comparison of immune function].

This paper deals with comparative study on the immune function of the tuberous root of Liriope spicata var. prolifera and Ophiopogon japonicus. The results showed that the aqueous extract of both species mentioned above could increase obviously the spleen weight (immunity organ) of mice, enhance the clearance rate of iv charcoal particles in mice and antagonize remarkably the leukopenia caused by cyclophosphamide.

Animals↗

Alteration of immune function following dietary mycotoxin exposure.

Mycotoxins are a group of structurally diverse fungal secondary metabolites that elicit a wide spectrum of toxicologic effects. Of particular interest is the capacity of some mycotoxins to alter normal immune function when present in foods at levels below observable overt toxicity. Aflatoxin, patulin, citrinin, and zearalenone experimentally alter immunity, and recent evidence suggests that the immunologic effects of ochratoxin A and trichothecenes may have particular significance to human and animal health. For example, the capacity of ochratoxin A to inhibit natural killer cell activity and increase growth of transplantable tumour cells has been associated with renal and hepatic carcinomas in mice and might similarly contribute to human cancer. Impaired resistance to pathogenic microorganisms occurs after exposure to the trichothecenes T-2 toxin and vomitoxin. This may predispose food animals to infectious disease and could result in decreased productivity as well as increased animal-to-human transmission of pathogens such as Salmonella and Listeria. Vomitoxin also alters normal mucosal immune function, specifically at the level of regulation of development, differentiation, and homing of IgA-producing plasma cells. Interestingly, vomitoxin-induced enhancement of IgA production in the systemic compartment contributes to manifestations in the mouse that are highly analogous to human IgA nephropathy, the most common form of human glomerulonephritis worldwide. Over the long term, the extrapolation of mycotoxin-induced immunologic effects observed in inbred mice to actual disease in livestock and humans will require investigations that both simulate natural exposure conditions as well as improve understanding of the cellular and molecular bases for these effects among different species.

Animals↗

Effects of dietary lipids on immune function in a murine sensitisation model.

We have tested the effect of dietary fatty acids on aspects of innate and specific adaptive T helper (Th) 1- and Th2-driven immune responses in a murine sensitisation model using dinitrochlorobenzene as sensitiser. Six groups of fifteen BALB/c mice were fed diets containing 30 % fat (by energy) for 8 weeks. Diets were rich in saturated fatty acids, n-6 polyunsaturated fatty acid (PUFA), or n-3 PUFA, each at a sufficient (11, 35 and 68 mg/kg) and a supplemented vitamin E level (1028, 1031 and 1030 mg/kg respectively). Feeding n-6 PUFA marginally decreased % phagocytosing cells at the low vitamin E level, but had no other effects on immune function. The n-3 PUFA diets decreased production of prostaglandin E2 while increasing oxidative burst and tumour necrosis factor alpha production. In addition adaptive Th1-driven responses (immunoglobulin, Ig)G2a, IgG2b, interferon-gamma:interleukin 4) were decreased, whereas Th2-driven and mucosal immune responses were increased (IgE) or unaffected (IgG1, IgA). Combination with high levels of alpha-tocopherol did not affect the reduced prostaglandin E2 production, augmented the increase of tumour necrosis factor alpha production and tended to ameliorate the selective suppressive effects of n-3 PUFA on certain Th1-driven effects (interferon-gamma:interleukin 4 ratio and IgG2a levels). We conclude that the sensitisation model appears useful for application in nutrition research. It allows a broad assessment of the effects of dietary intervention on various aspects of immune responsiveness, and as such provides a valuable model to assess, characterise and rank effects of foods and/or nutrients on a range of immune functions, including Th1-Th2 polarisation.

Animals↗

Nonsuppression of cortisol in depression and immune function.

Eighteen depressive patients and twenty-five healthy control subjects were studied using a comprehensive immunological test system and the dexamethasone suppression test (DST) as well as some additional neuroendocrine parameters. In addition, immune functions of six of the patients were studied serially three times at 1-2 month's intervals. The OKT 4+/8+ ratio (OKT 4+ = helper/inducer phenotype; OKT 8+ = suppressor/cytotoxic phenotype) was slightly higher in those ten depressive patients showing suppression in the DST than in healthy controls, but there were no significant differences between the nonsuppressor and suppressor groups or between the nonsuppressor and suppressor groups or between nonsuppressors and control subjects. Lymphocyte transformation responses induced by phytohaemagglutinin (PHA) were similar in the nonsuppressors and suppressors, but lower in both groups than in control subjects. The number of Ig-secreting cells measured in the absence and presence of pokeweed mitogen (PWM) were similar in the nonsuppressor and suppressor groups. Four of the depressive patients tested repeatedly exhibited an abnormal response in the DST at the beginning of the study. During the follow-up period two of them recovered completely from depression as well as the patients with a normal suppression in the DST. The proportions of T and B lymphocytes and regulatory T lymphocyte subsets as well as the functions of T and B lymphocytes of the nonsuppressors and suppressors in the DST were within normal ranges before and after recovery from depression and comparable to healthy controls in repeated testing. The results indicate that in spite of the importance of cortisol in immunoregulation, the increased cortisol secretion and typical resistance to dexamethasone suppression in endogenously depressive patients is not profoundly and consistently reflected in immune functions. Neither does normalization of cortisol responses induce any major changes in immune status during a patient's recovery from depression. Previous work indicates that suppressed immunity may play an important role in the increased morbidity and mortality associated with bereavement. In the light of present findings we suggest that endogenous depression differs also in this respect from grief reactions.

Adult↗

L-arginine: a unique amino acid for improving depressed wound immune function following hemorrhage.

OBJECTIVE: To determine whether L-arginine has any salutary effects on wound immune cell function following trauma-hemorrhage. BACKGROUND: Depressed wound immune function contributes to an increased incidence of wound infections following hemorrhage. Although administration of L-arginine has been shown to restore depressed cell-mediated immune responses following hemorrhage potentially by maintaining organ blood flow, it remains unknown whether L-arginine has any salutary effects on the depressed local immune response at the wound site. METHODS: Male mice were subjected to a midline laparotomy and polyvinyl sponges were implanted subcutaneously in the abdominal wound prior to hemorrhage (35 +/- 5 mm Hg for 90 min and resuscitation) or sham operation. During resuscitation mice received 300 mg/kg body weight L-arginine or saline (vehicle). Sponges were harvested 24 h thereafter, wound fluid collected and wound immune cells cultured for 24 h in the presence of LPS. Pro- (IL-1 beta, IL-6) and anti-inflammatory (IL-10) cytokines were determined in the supernatants and the wound fluid. In addition, wounds were stained for IL-6 immunohistochemically. In a separate set of animals, skin and muscle blood flow was determined by microspheres. RESULTS: The capacity of wound immune cells to release IL-1 beta and IL-6 in vitro was significantly depressed in hemorrhaged mice receiving vehicle. Administration of L-arginine, however, improved wound immune cell function. In contrast, in vivo the increased IL-6 release at the wound site was decreased in L-arginine-treated mice following hemorrhage. Moreover, IL-10 levels were significantly increased in the wound fluid in hemorrhaged animals receiving L-arginine compared to vehicle-treated mice. In addition, the depressed skin and muscle blood flow after hemorrhage was restored by L-arginine. CONCLUSIONS: Thus, L-arginine might improve local wound cell function by decreasing the inflammatory response at the wound site. Since L-arginine protected wound immune cell function this amino acid might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications following hemorrhage.

Animals↗

Brazilin modulates immune function mainly by augmenting T cell activity in halothane administered mice.

Previously we reported that brazilin, the main principle of Caesalpinia sappan, was able to improve the altered immune functions caused by halothane administration in mice. To elucidate the mechanisms of its immunomodulating activities, the effects of brazilin on the functions of T cells and splenic cellularity were investigated. Brazilin decreased splenic cellularity and IL-2 production which had been augmented in mice treated with halothane (21.5% in olive oil, 10 mmol/kg) for 4 consecutive days whereas the reduced expression of IL-2 receptors by ConA or standard IL-2 was increased by brazilin treatment. These data indicate that halothane induced a dysfunction of T cells resulting in abnormal immune responses and these altered immune functions might be improved mainly by affecting the function of T cells.

Animals↗

Aging, nutrition and immune function.

Aging is usually associated with increase in chronic disease as well as infections and associated morbidity. This is often thought to be secondary to immunosenescence. Whether this decline in immune function with aging is due to the aging process per se or is secondary to poor health, inflammation, and other life style factors particularly suboptimal nutritional status is discussed. Aging is often associated with dysregulation of immune response even among healthy elderly; some of these changes may be secondary to deficiencies of macronutrients (energy and protein) and micronutrients (notably, vitamins B6, B12, and folic acid as well as iron and zinc). Older individuals often have multiple nutrient deficiencies because of physiological, social and economic factors. Nutrient supplementation is often accompanied by an improvement in immune function particularly in those who are nutrient-deficient. The long-term benefits of multinutrient supplements to healthy elderly not at risk for nutrient deficiencies, however, are currently not well-established. Priorities for future research and methodological considerations for future studies are discussed.

Aged↗

Immune functions, clinical parameters and hormone receptor status in breast cancer patients.

We have carried out a detailed analysis of the cellular immune functions of breast cancer patients in comparison with healthy controls. A possible correlation between immune and clinical parameters was analysed in 50 breast cancer patients. Immune parameters, natural killer cell and T lymphocyte functions and the numbers of circulating T lymphocytes were analysed against the clinical parameters comprising the tumour burden, the stage of the disease and the expression of hormone receptors on the tumour. In order to analyse the immune function data effectively, low responders were identified with stringent cut-off values. Considerably higher proportions of low responders were found among the patient population. Elevated numbers of circulating T lymphocytes and CD3-directed cytolysis correlated with the expression of oestrogen receptors independently of the clinical/histological parameters.

Adult↗