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Effect of olive oil on immune function in middle-aged men.

Consumption of diets rich in monounsaturated fatty acids (MUFAs) has been linked with a low prevalence of atherosclerosis and there has been great interest in the effects of MUFAs on lipoprotein metabolism. Less attention has been paid to the effects of MUFAs on the immune system, yet cells of the immune system are an inherent part of the inflammatory events involved in atherosclerosis and several animal studies showed that olive oil has some potent immunomodulatory actions. We therefore considered it important to investigate the effects of chronic consumption of MUFAs on several immune cell functions in healthy humans. Healthy middle-aged males entered a double-blind, randomized, controlled trial in which they consumed either a MUFA diet or a control diet for 2 mo. There was a significant decrease in the expression of intercellular adhesion molecule 1 by peripheral blood mononuclear cells from subjects consuming the MUFA diet. Consumption of the MUFA diet did not affect natural killer cell activity or proliferation of mitogen-stimulated leukocytes. The effects of a MUFA-rich diet on adhesion molecule expression may have implications for the influence of dietary fat on inflammatory diseases, including atherosclerosis.

Adult↗

Effects of treated sewage effluent on immune function in rainbow trout (Oncorhynchus mykiss).

In this study, the immune reactions of rainbow trout (Oncorhynchus mykiss) were examined, after exposure to 10, 30 and 70% of tertiary-treated municipal sewage effluent for 27 days. Exposures were conducted concurrently with and without an immune challenge using intraperitoneal injections of inactivated Aeromonas salmonicida salmonicida. Due to the time required to prepare and analyse samples, fish sampling was conducted over two consecutive days. There was no trout mortality for any of the experimental treatments. The exposure to effluent increased in vitro lymphocyte proliferation, decreased circulating lymphocytes and increased degrading erythrocytes in peripheral blood samples. Circulating lymphocytes were only decreased in the sham-injected, but not in the A. salmonicida-injected group. In addition to effluent effects, circulating lymphocytes and lymphocyte proliferation were decreased on day 2 of sampling as compared to day 1. Concentration-dependent degradation of erythrocytes was only observed on day 2 of sampling. Capture and removal of trout on day 1 of sampling presumably caused low-level stress that affected some results on day 2. Oxidative burst, phagocytosis, lysozyme, leucocyte populations other than lymphocytes and A. salmonicida-specific IgM production were not affected by exposure to effluent, and of these parameters, only oxidative burst and total leucocytes showed sampling day effects. From these results it can be observed, that with the exception of oxidative burst, those variables affected by effluent exposure were also significantly changed by the low-level sampling stress imposed by staggered sampling. Elevated liver mixed-function oxygenase activity as measured by 7-ethoxyresorufin-O-deethylase activity, and increased bile polycyclic aromatic hydrocarbon (PAH) metabolites were observed in response to sewage effluent exposure. As both PAHs and stress are known immune suppressors, it is difficult to conclude whether or not changes in immune parameters due to effluent exposure were caused by the direct action of chemicals, or were due to a general stress response.

Aeromonas salmonicida↗

Evaluation of carnitine, acetylcarnitine and isovalerylcarnitine on immune function and apoptosis.

The pool of different carnitine derivatives is formed by carnitine, acetylcarnitine, propionylcarnitine and isovalerylcarnitine. Isovalerylcarnitine is a compound performing activities that differ from those of the other carnitine esters. Its activity on proteolytic enzymes and on the calpain system has been demonstrated in the past. Both the calpain and the caspase systems belong to the protease family and lead to cytochrome activation and apoptosis. The two systems can interact to promote apoptosis. In view of this proapoptotic activity of isovalerylcarnitine, studies were carried out to ascertain whether this carnitine derivative influences cell-reaction processes associated with apoptosis. U937 leukemic cells were selected for these studies because they are a well-established model for the assessment of cellular immune responses. In addition to nuclear morphologic alterations produced by apoptosis that can be detected by specific histochemical and microscopic methods, we also took other cell functions into consideration, such as phagocytosis, cell killing and cell growth, which are indices of immune function related to apoptosis. Unlike reference carnitine forms, isovalerylcarnitine produced an early and marked increase in phagocytosis and also an increase in cell killing. Cell proliferation was reduced. The hypothesis is set forth that isovalerylcarnitine may be a caspase-activating, proapoptotic factor that resembles various anticancer agents, which induce early apoptosis that coincides with early activation of caspase. This hypothesis is supported by the ability of isovalerylcarnitine to induce early phagocytosis and cell killing.

Acetylcarnitine↗

Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice.

Atrazine (ATZ) is used throughout North America to control annual broadleaf weeds and grasses in various crops including; corn, sorghum, and sugar cane. Unfortunately, contamination of surface and ground water has occurred as a result of ATZ's chemical and physical properties, and its widespread use throughout the U.S. Midwest. A study of ATZ's immunomodulatory properties was conducted using female B6C3F1 mice and a panel of immune assays and host resistance models designed to evaluate cell-mediated and antibody-mediated immunity. Mice were administered ATZ by gavage (0, 24, 250, and 500 mg/kg/day) for 14 days then evaluated for immune responsiveness. ATZ treatment significantly increased the number of splenic CD8+ T cells, cytotoxic T cell and mixed leukocyte responses, and dose-dependently reduced host resistance to B16F10 melanoma. Thymus and spleen weights, total spleen cell numbers and fixed macrophage function was also reduced in mice that were exposed to ATZ. These results demonstrate that oral ATZ exposure is sufficient to alter cell-mediated immune function and disease resistance in female B6C3F1 mice.

Administration, Oral↗

Effects of nicotine on the hypothalamic-pituitary-axis (HPA) and immune function: introduction to the Sixth Nicotine Round Table Satellite, American Society of Addiction Medicine Nicotine Dependence Meeting, November 15, 1997.

This meeting was the sixth consecutive Nicotine Round Table Satellite Meeting which was held in Washington, DC, on 15 November, 1996; previous meetings are presented in Table I. The overall objective of these meetings was to bring together scientists and clinicians as a means of developing a dialogue concerning the basic mechanisms of nicotine action and the effects of nicotine on the whole organism. The specific topic of this meeting was chosen because of the potent effects of nicotine on the hypothalamic-pituitary-axis (HPA), and newer concepts indicating that the immune system and the HPA are connected via a variety of neuroendocrine and neurotransmitter elements. Whereas the HPA appears to play a unique role in adapting to internal and external stressors, the immune system appears to act as a forward scout which provides information important to the HPA. This Satellite Meeting evaluated the effects of nicotine from three points of view: (1) the effects of nicotine on HPA function; (2) the effects of the HPA on the pharmacological effects of nicotine; and (3) the effects of nicotine on immune function. This specific presentation will provide an overview of the findings of the meeting and will discuss several of the overriding issues in this area of nicotine research.

Animals↗

Is hypothalamic GABA involved in immune function in relation to dietary protein during aging?

Hypothalamic GABAergic activity and immune response in spleen were not significantly changed with the increase of age from 3 to 6 months in adult male albino rats. Further increase of age from 6 to 9 months increase the GABAergic activity and decreased the cell viability in spleen without any change in its T-lymphocyte cytotoxicity. Consumption of low protein diet (LPD) for a short-term period (STP; 7 consecutive days) increased the hypothalamic GABAergic activity without changing the immune response in 3 months old rats. When supplemented for a long-term period (LTP; 30 consecutive days) to 3 months old rats, a reduction of hypothalamic GABAergic activity and the immune response was observed. Intake of high protein diet (HPD) for both STP and LTP increased the GABAergic activity and immune response, but the increase of GABAergic activity in hypothalamus under STP was greater than that observed under LTP. In 6 months old rats consumption of LPD for STP reduced the GABAergic activity without any alteration of its immune response. Long-term supplementation of this LPD to the same age group increased GABAergic activity and the mitotic activity of spleen cells without any alteration of the functional activity of the T-cells in spleen. Consumption of HPD for STP failed to produce any change in hypothalamic GABAergic activity and the immune response of 6 months old rats. Supplementation of HPD for LTP reduced the hypothalamic GABAergic activity and the immune response of the same age group. The reduction in hypothalamic GABAergic activity without any change in the immune response was observed following the supplementation of low protein diet to 9 months old rat for STP. Intake of the LPD for LTP also reduced the hypothalamic GABAergic activity and the mitotic activity of the spleen cells without any alteration of the functional activity of the T-cells in spleen of 9 months old rats. Supplementation of HPD for STP to this aged rat, on the other hand, failed to produced any change in hypothalamic GABAergic activity and the immune response. Intake of HPD for LTP by this aged rats increased the hypothalamic GABAergic activity along with the immune response. The results of this study, thus, suggest that hypothalamic GABAergic activity during aging is an index of immune response and it is modulated following the short- and long-term consumption of protein poor and protein rich diet.

Aging↗

Immune functions and the prognosis of patients with solid tumours.

The immune competence of 169 patients with solid malignant tumours was assessed before initiation of radiotherapy or chemotherapy and followed during the course of the disease. The data of years 1974-1984 were collected and subjected to an analysis in order to evaluate their prognostic significance. The number of leucocytes and lymphocytes in the peripheral blood, the percentage or absolute number of E-rosette forming cells or EAC-rosette forming cells or serum immunoglobulin levels did not show any association with the prognosis. Lymphocyte proliferative responses to PHA, Con A and PPD as studied before initiation of the treatment did not correlate with recurrence or final prognosis of the disease, except that the responses to PPD were slightly lower in patients with recurrence of gynaecological cancer, melanoma or gastrointestinal cancer than in their respective control patients. In the values observed after the first treatment course a low response to PPD was associated with poor prognosis in patients with melanoma or gastrointestinal cancer. At the time of recurrent disease the PPD response showed an association with a poor final outcome in patients with gastrointestinal malignancy. Of the responses assessed less than 3 months before death due to cancer, only in patients with breast cancer were low Con A responses seen; in all patient groups the PHA responses decreased in the terminal patients. The results do not support the idea that the methods currently available should be routinely used in the follow-up of cancer patients; rather, they indicate the need to seek new methods for this purpose.

Adolescent↗

[Effect on morphine and other opioids on immune function].

PROBLEM: Already 1898 first clinical observations of a possible immune suppression after morphine intake were published. Today there are many reports describing opioid effects on nearly all parameters of the immune system. The question arises, whether there exists any evidence for clinical (harming) effects on patients. METHOD: Recent experimental and clinical publications are reviewed. Results are summarized, pathophysiological mechanisms and clinical conclusions discussed. RESULTS: Morphine and other opioids have immunomodulating effects on nearly all measurable parts of the immune system (macrophages, granulocytes, nk-cells; mediators like Interleukin 1, 2 and 6, TNF). However, most studies did not include pain models, and in addition, high morphine doses were used. First studies using a combined pain/morphine-approach report immune stimulating effects. There are three pathophysiological mechanisms under discussion, including opioid receptors on immune competent cells, central opioid receptors activating the adrenergic system and opioid-induced steroid release with consecutive immunosuppression. It is completely unclear, if there is any relevance of these findings for clinical settings. CONCLUSIONS: The question whether use of opioids can harm chronic pain patients is unsolved. There is an urgent need for studies in clinical settings with clinical relevant parameters.

English Abstract↗

Disordered immune function in patients with polyglandular failure.

A standard assessment of immunity was accomplished in 15 patients with the polyglandular failure syndrome and compared to similar studies in appropriate healthy controls. The patients exhibited decreased delayed cutaneous responsiveness and increased serum levels of immunoglobulins G and A. Complement fixing antibody titers to a number of common viruses were equivalent to those observed in controls, but titers ot Coxsackie B4 and B5 viruses were decreased in patients. The decreased antibody titers to Coxsackie B4 and B5 represent an alteration in host protection which is of possible importance in the etiology of polyglandular failure.

Antibodies, Viral↗

Immune function risk factors for acute lower respiratory tract infections.

The immune response of pneumonia patients and controls to Streptococcus pneumoniae was investigated by enzyme-linked immunosorbent assay (ELISA). Patients less than 6 months of age had significantly lower levels of anti-pneumococcal polysaccharide antibodies than their age-matched controls. Patients and controls 6-14 months of age had lower antibody levels than the children 0-5 months of age. Adult patients and controls did not differ in their antibody status. However, patients and Papua New Guinean controls had depressed cell-mediated immunity and low T-cell numbers. Low levels of antibodies to pneumococcal polysaccharides in children less than 6 months of age appear to be an important risk factor for acute lower respiratory tract infections but other factors may be important in older infants and adults.

Acute Disease↗

Differential stimulation of immune function by respiratory and contact chemical allergens.

The nature of immune responses induced following topical exposure to 2,4-dinitrochlorobenzene (DNCB), a potent contact allergen which lacks the capacity to cause respiratory sensitization, and trimellitic anhydride (TMA), a respiratory allergen with comparatively weak skin-sensitizing potential, have been investigated. Exposure of BALB/c strain mice to concentrations of TMA and DNCB which resulted in equivalent levels of activation (cell proliferation) in lymph nodes draining the site of application (50% TMA and 1% DNCB) induced comparable levels of contact sensitization and IgG anti-hapten antibody production. However, under these conditions, exposure only to TMA resulted in an elevation of serum IgE. Furthermore, while TMA induced IgG2b rather than IgG2a antibody the reverse pattern was observed with DNCB. These data demonstrate that TMA and DNCB elicit qualitatively different immune responses which are consistent with their potential to cause respiratory and contact allergy, respectively. The possibility that the responses induced by these chemicals reflect a differential stimulation of T-helper cell subsets (Th1 and Th2) is discussed.

Allergens↗

[Pharmacological modification of prolactinemia. Effects on cellular immune function in normal subjects].

Prolactin markedly influences cellular and humoral immunity in animals, but there is little information on its role in men. The aim of this work was to study the immune effects of pharmacological modification of prolactin levels in 5 healthy individuals. Peripheral blood mononuclear cell proliferative response to mitogens and antigens, interleukin-2 (IL-2) production, soluble and membrane IL-2 receptor expression in peripheral blood mononuclear cells and serum soluble IL-2 receptors were successively measured during normoprolactinemia, during bromocriptine induced hypoprolactinemia and during metoclopramide induced hyperprolactinemia. There was a significant increase in cellular proliferation during hypoprolactinemia when compared with hyperprolactinemia. No concomitant changes in soluble or membrane receptor expression or IL-2 production were observed. It is concluded that lymphocyte proliferative response to mitogens is dependent on prolactin levels in man and that this effects is not mediated by IL-2 or its receptors. These results may be potentially relevant in clinic since changes in serum prolactin have been described in different autoimmune diseases.

Adult↗

Interleukin 12: a key modulator of immune function.

Interleukin (IL)-12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells. With further understanding of its activities, IL-12 has emerged as an important cytokine, affecting both immune and hematologic functions. It has been shown to be necessary for the T cell independent induction of interferon (IFN)-gamma, critical for the initial suppression of bacterial and parasitic infection; for the development of a Th1 response, critical for effective host defense against intracellular pathogens; and for the activation of differentiated T lymphocytes of both CD4+ and CD8+ phenotype. IL-12 thus functions to activate and to link the innate and acquired immune responses. The therapeutic potential of these activities is suggested by studies in tumor and microbial models. IL-12 has suppressed tumor growth in all murine models examined. Antimicrobial activity has been demonstrated in bacterial, yeast, parasitic, and viral models of infection. In many of these models, activity has been linked to production of IFN-gamma and, in the parasite model, to development of a Th1 response. In addition to the therapeutic potential associated with IL-12 activity in these disease models, the understanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL-4 and IL-10, has clarified and extended our understanding of immune regulation and should lead to significant developments in understanding the progression of AIDS and the development of vaccine adjuvants able to direct the immune response.

Animals↗

Effects of examination stress on some cellular immunity functions.

The effects of examination stress on some lymphocyte subpopulations and cellular immune responses are reported. Twelve undergraduate students of psychology in examination term were tested six weeks before the written examination (phase I), one day before the first or second examination day (phase II) and 12-14 days after the examination (phase III). A comparable control group of students not in examination was assessed in parallel in phase II. The percentage of circulating monocytes increased in phase II in the examination group whereas the percentage of large (probably activated) CD4 and CD8 cells decreased. There was also a decrease in the number of cells expressing the IL-2 receptor in phase II. The proliferative response of T-cells to antigens, mitogens and allogeneic cells decreased from phase I to phase III. Thus, acute examination stress has a detectable influence on certain cellular immunological functions.

Adult↗

Species comparison of anatomical and functional immune system development.

The components of the immune system have not been traditionally emphasized as potential target organs in standard developmental and reproductive toxicity (DART) protocols. A number of workshops have been organized in recent years to examine scientific questions that underlie developmental immunotoxicity tests, and the interpretation of results as they relate to human risk assessment. A key question that must be addressed is to determine the most appropriate species and strains to model the developing human immune system. The objective of this review is to compare the anatomical and functional development of the immune system in several species important to either preclinical studies for drug development or safety assessments for chemicals, with what is known in humans. The development of the immune system in humans will be compared to what is known in mice, rats, dogs and nonhuman primates.

Age Distribution↗