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Use of the local lymph node assay in assessment of immune function.

The murine local lymph node assay (LLNA) was originally developed as a predictive test method for the identification of chemicals with sensitizing potential. In this study we demonstrated that an adapted LLNA can also be used as an immune function assay by studying the effects of orally administered immunomodulating compounds on the T-cell-dependent immune response induced by the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph nodes (LNs) after DNCB application on both ears. Immunosuppression induced by CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA. Cytokine release measurements proved valuable to confirm the results of the cell proliferation assay and to obtain an indication of the effect on Th1/Th2 balance. We believe to have demonstrated the applicability of an adapted LLNA as an immune function assay in the mouse.

Administration, Oral↗

[Analysis on the traditional Chinese medicine syndromes of the patients with autoimmune thyroid diseases. Changes in the thyroid and immune functions in 109 cases].

Eighty-nine cases of hyperthyroidism and 20 cases of hypothyroidism caused by Hashimoto's thyroiditis were observed in order to analyse the thyroid and immune functions of the patients, and their relationship with the syndromes of TCM. The results showed that, in the patients with Yin deficiency syndrome, the contents of total T4, T3 were higher than normal and TSH lower than normal, while in Yang deficient patients, the contents of total T4, T3 were lower than normal and TSH higher than normal. This results suggested that the states of thyroid functions were closely related to the TCM syndromes. It was also found that the percentage of OKT 4+ cells and the self-recognizing ability of lymphocytes were lower than normal in patients with hyperthyroidism and Yin deficiency. While in patients with hypothyroidism and Yang deficiency, they were higher than normal. These meant that the abilities of lymphocyte autoreaction in Yin deficient patients were in contrary tendency with those in Yang deficient patients. The former had the manifestation of over-inhibition while the latter, hyperaction. Besides, the contents of auto-antibodies were higher than normal in both the patients with hyperthyroidism and hypothyroidism, which manifested itself as a common character of autoimmune thyroid diseases. The results indicated that there were common characters as well as individual characters of thyroid and immune functions between hyperthyroid patients and hypothyroid patients, and these characters might well be the material bases of various syndromes in TCM.

Adult↗

Modulation of immune function by intestinal neuropeptides.

Direct regulatory control of the immune system by the central nervous system has been postulated. In support of this view is a large body of literature describing immunoregulatory activities of neuropeptides isolated from the gastrointestinal tract. In this review we examine the evidence for expression of specific receptors for gut peptides on immune effector cells and further explore the regulatory effects of these peptides on immune function. Peptides to be discussed include substance P, somatostatin, vasoactive intestinal peptide (VIP), the opioid peptides leu and met enkephalin, calcitonin gene related peptide (CGRP), neuropeptide Y, and cholecystokinin (CCK).

Calcitonin Gene-Related Peptide↗

Effects of morphine and its metabolites on immune function in advanced cancer patients.

STUDY OBJECTIVE: To determine whether morphine and its active metabolites such as morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune function in patients with advanced cancer who required morphine for pain relief. DESIGN: Prospective observational clinical study. SETTING: Pain clinic of a university hospital. PATIENTS: Fifteen patients who visited our clinic for control of advanced cancer pain. INTERVENTIONS: During the initiation or changes of morphine therapy, venous blood samples were obtained at the enrollment of this study, 1 and 3 weeks after the change of morphine dose or route. MEASUREMENTS: Lymphocyte subpopulation CD4+ and CD8+, activity of natural killer cell, phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin M and G concentrations were measured, as well as plasma concentrations of morphine, M-3-G, and M-6-G. MAIN RESULTS: At the entry of the study, 6 patients did not receive any type of morphine medication (group 1), whereas 9 patients were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the entry period, was reduced to 2 of 10 (visual analogue scale) during the study periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were significantly less than those in Group 2, plasma concentrations of immunologic markers were similar between the groups. In Group 1, Spearman linear regression analysis showed negative correlation between morphine-derived metabolites and immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was found with all immunologic parameters in Group 2. Stepwise linear regression analyses showed that the metabolites, rather than morphine per se, modulated immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin G concentration in Group 1. CONCLUSIONS: The present study suggests that some of humoral and cellular immunity are modulated by morphine-derived metabolites at the early phase of morphine therapy in patients with advanced cancer.

Adult↗

Physical activity and immune function in elderly women.

The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Progressive multiple sclerosis: abnormal immune functions in vitro and aberrant correlation with enumeration of lymphocyte subpopulations.

In a series of 27 consecutive progressive multiple sclerosis (MS) patients under age 50 we have simultaneously measured 3 in vitro immune functions and 6 markers and compared their results to a group of 21 controls. We have confirmed a reduction of concanavalin A (Con A) -induced suppression and NK function contrasting with increased IgG secretion in response to pokeweed mitogen (PWM). Among 6 monoclonal antibody-recognized subpopulation (Leu 1, Leu 2, OKT8, Leu 3, Leu 7 and Leu 11) only Leu 2+ lymphocytes were statistically reduced. OKT8+ were slightly reduced, Leu 3+ were slightly increased. Discriminant analysis revealed that the 3 immune functions together with the results of OKT8 and Leu 3 enumeration were sufficient to appropriately classify most of the individuals. Only 3 MS and 4 controls were misclassified. Correlation analysis suggested disappearance of the doubly labelled OKT8/Leu 7 population in MS patients. In MS as opposed to controls Con A-induced suppression did not correlate with suppressor cell markers but correlated with NK cell markers suggesting that in MS this population mediates Con A-induced suppression. IgG secretion and Con A suppressor cell function were inversely correlated in MS patients but not in controls, suggesting that in chronic progressive multiple sclerosis a common abnormality underlies both increased response to PWM and decreased induction of suppression by Con A.

Adult↗

Effect of human urinary macrophage colony-stimulating factor on the immune functions and the blood cell counts in patients with ovarian carcinoma receiving cytotoxic chemotherapy.

The present study investigated the effect of macrophage colony-stimulating factor (M-CSF) on the immune functions and blood cell counts of patients with ovarian carcinoma receiving cytotoxic chemotherapy (CTX). Seventy-five consecutive patients with white blood cell counts less than 3,000/microl after CTX were randomly assigned to receive either M-CSF (human urinary macrophage colony-stimulating factor: hM-CSF, 8x106 U as 7-day intravenous infusions) or no treatment. Immune assays in addition to routine peripheral blood examinations were performed on these patients at various time points. hM-CSF dosing significantly increased monocyte, lymphocyte, granulocyte, and platelet counts that were decreased by CTX. hM-CSF also significantly enhanced lymphokine-activated killer and natural killer activities, which was accompanied by a significantly augmented interleukin (IL)-2 production. Interestingly, IL-2 production was enhanced by hM-CSF dosing in 24 of the 27 patients with a pre-hM-CSF level of IL-2 below 10 U/ml, but such an effect was not observed in nine of the 10 patients having a basal value of 10 U/ml or higher. Thus, hM-CSF is considered to be a cytokine that can augment or regulate immune functions impaired by CTX and increase blood cell counts that are decreased by CTX.

Antineoplastic Combined Chemotherapy Protocols↗

Immune functions of veal calves fed low amounts of iron.

Immune functions were studied in male calves fed milk replacer (MR) containing 10 or 50 mg iron (Fe)/kg. Calves fed 10 mg Fe/kg MR developed marked hypoferremia and anemia, whereas serum-Fe and haemoglobin concentration of calves fed 50 mg Fe/kg MR were normal. Growth performance was reduced, while feed/gain ratio, incidence of infections (especially pneumonias), febrile body temperatures and antibiotic treatments were higher in calves fed 10 than 50 mg Fe/kg MR (p < 0.05). Whereas antibody production (to horse erythrocytes) and lymphocyte stimulation (by mitogens) were not significantly altered, cell-mediated immunity (measured as cutaneous delayed-type hypersensitivity reaction to dinitrofluoro-benzene), number of neutrophils with phagocytic capacity, activity of the Fe-containing enzyme myeloperoxidase, blood serum IgG concentration and the number and diameter of germinal centres as a measure of the number and production of B-cells in cervical superficial lymph nodes in calves fed 10 mg Fe/kg MR were reduced when compared with calves fed 50 mg Fe/kg MR (p < 0.05). In conclusion, severe Fe deficiency caused reduced growth performance, associated with and partly due to higher incidence of infections because of defective immune reactions.

Animals↗

Effect of dietary fiber on the lipid metabolism and immune function of aged Sprague-Dawley rats.

Eight-month-old Sprague-Dawley rats were fed on diets containing dietary fiber at the 5% level for 3 weeks to examine the effect on the lipid metabolism and immune function. Among cellulose, guar gum, partially hydrolyzed guar gum (PHGG), glucomannan and highly methoxylated pectin, guar gum induced a significant decrease in the food intake and weight gain, as well as a significant increase in the liver weight. In addition, the epidydimal adipose tissue weight of the rats fed on PHGG was significantly higher than that of the rats fed on cellulose. There was no significant effect on the serum lipid levels, but the serum IgG level of the rats fed on guar gum was significantly lower than that of the rats fed on cellulose. The IgA and IgG productivity in mesenteric lymph node (MLN) lymphocytes was significantly higher in the rats fed on guar gum, glucomannan and pectin than in those fed on cellulose, while the effect on Ig productivity in spleen lymphocytes was not as marked. In addition, only guar gum induced a significant increase of IgM productivity in MLN lymphocytes when compared to the cellulose group. These results suggest that enhancement of the immune function by dietary fiber is mainly expressed in the gut immune system.

Aging↗

Neonatal handling of Amazon parrots alters the stress response and immune function.

The influence of neonatal handling on behavior and immune function was assessed in Orange-winged Amazon parrots (Amazona amazonica). Chicks (n=11) were gently handled daily from 25 days of age until 38 days post-fledging, while control chicks (n=9) were not handled. At 10 days post-fledging ( approximately 66 days of age), chicks were given tests to evaluate tameness (e.g., willingness to perch on an offered finger). They were then restrained for 10 min, either by being held while perching (handled group) or, because they would not perch, by being restrained in a towel (nonhandled group). Serum corticosterone levels were measured and immune status was assessed by: the delayed-type hypersensitivity (DTH) response to phytohemagglutinin-P (PH-P) injection; the humoral response to a killed Newcastle disease virus (NDV) challenge; and heterophil:lymphocyte ratio (H:L). Handled chicks were tamer by all measures of tameness. DTH was greater in nonhandled chicks (P</=0.002), as were serum corticosterone levels (Wilcoxon, P</=0.05), while NDV antibody titers were possibly reduced (P</=0.09). H:L ratios did not differ. We conclude that handling conditioned the birds to be held in a manner that appeared not to be stressful. The greater DTH response of nonhandled chicks suggests that either their DTH response was enhanced by the acute stress of being restrained in a towel, and/or the DTH response of handled chicks was suppressed as a result of the repeated physiologic stress from handling during the neonatal period. In either event, handling produced marked differences in response to types of restraint that would be typically encountered in the husbandry of Amazons in captivity.

Journal Article↗

Multiple immune functions in rats fed Echinacea extracts.

This study evaluated acquired-immune functions representing the three major branches of the immune system in male rats fed a commercially available echinacea product. An additional comparison of effects on antibody formation in male and female rats was done using the commercial echinacea product and two echinacea tinctures marketed by local herbalists. In initial testing, we found no evidence of altered natural killer cell activity, T cell-mediated delayed-type hypersensitivity, or specific antibody formation in male rats given either a 225 mg/kg or 50 mg/kg of the commercial echinacea for 6 weeks. Antibody formation was significantly suppressed in female but not male rats given 250 mg/kg for 2 weeks of the commercial echinacea. The local products tested had no effect on antibody formation. We concluded that our study provided no supporting evidence for immunostimulatory activity by the echinacea preparations we examined and, in fact, may be immunosuppressive under some conditions.

Adjuvants, Immunologic↗

Immune function in healthy relatives of patients with malignant disease.

Immune function studies of healthy members of families with multiple lymphoreticular neoplasms were compared with those of healthy members of families with multiple cancers and families with no known history of cancer. The lymphoma family group had a significantly elevated serum level of IgM and diminished responses to the Candida albicans skin test antigen and the T-cell mitogen concanavalin A. Subjects with Epstein-Barr virus-viral capsid antigen titers greater than or equal to 160 had lower responses to mitogens.

Adolescent↗

Stimulation of non-specific immune functions in seawater-acclimated rainbow trout, Oncorhynchus mykiss, with reference to the role of growth hormone.

The influence of acclimation to seawater (SW) and growth hormone (GH) administration on immune functions was examined in the rainbow trout (Oncorhynchus mykiss). After 3 days acclimation to dilute SW (12 parts per thousand, ppt), an increase in plasma lysozyme activity was observed compared to the fish kept in fresh water (FW). No change was seen in plasma immunoglobulin M (IgM) levels. When they were transferred from dilute SW to full-strength SW (29 ppt) after a single intra-peritoneal injection of ovine or salmon GH, plasma sodium levels of GH-treated fish were significantly lower than those of the control fish injected with Ringer's solution 24 h after the transfer. The plasma level of IgM was not influenced by GH injection in the fish kept in FW nor in those transferred to SW. The administration of GH increased plasma lysozyme activity in the fish in FW, but no further increase was seen after SW transfer. The production of superoxide anions in peripheral blood leucocytes was stimulated by GH in both FW and SW. These results suggest that GH is involved in the stimulation of the non-specific immune functions in SW-acclimated salmonids.

Adaptation, Physiological↗

Adolescent nicotine: deficits in immune function.

Maternal cigarette smoking during pregnancy is known to alter immune function in the offspring and recent studies with animals indicate that prenatal nicotine exposure leads to lasting deficiencies in T-lymphocyte mitogenic responses, likely through excessive cholinergic stimulation during a critical stage of development. The current study was conducted to determine if the vulnerable period for nicotine-induced mis-programming of immune responses extends into adolescence, the stage at which most smokers begin tobacco use. Adolescent rats were given nicotine via osmotic minipump infusions on postnatal days (PN) 30-47.5, using a regimen that produces plasma levels (25 ng/ml) of nicotine similar to those in smokers or in users of transdermal nicotine patches. Toward the end of the infusion period (PN45) and 1 month after termination of nicotine exposure (PN80), we examined the mitogenic responses of splenocytes to Concanavalin A. Although no deficiencies were seen on PN45, there were robust decreases in mitogenic responses on PN80, with deficits apparent at both suboptimal and optimal concentrations of Concanavalin A. These results indicate that the adolescent immune system is vulnerable to nicotine-induced disruption of T-cell function.

Age Factors↗

Arginine stimulates wound healing and immune function in elderly human beings.

BACKGROUND: Experimentally, arginine enhances immune function and promotes wound healing. In this randomized double-blind study we investigated the effect of oral arginine supplementation on wound healing and T-cell function in elderly human beings (more than 65 years of age). METHODS: Thirty elderly, healthy, human volunteers (15 men and 15 women) received daily supplements of 30 gm arginine aspartate (17 gm free arginine). Fifteen volunteers (nine men and six women) received a placebo syrup. Fibroplastic wound responses were assessed by inserting a polytetrafluoroethylene catheter subcutaneously into the right deltoid region. Epithelialization was examined by creating a 2 x 2 cm split thickness wound on the lateral aspect of the upper thigh. Mitogenic response of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and allogeneic stimuli was assayed at the beginning and end of supplementation. Polytetrafluoroethylene catheters were analyzed for alpha-amino nitrogen (assessment of total protein accumulation), hydroxyproline (index of reparative collagen synthesis), and DNA accumulation (index of cellular infiltration). RESULTS: Arginine supplementation for 2 weeks significantly enhanced wound catheter hydroxyproline accumulation (26.49 +/- 2.39 nmol/cm vs 17.41 +/- 2.04 nmol/cm) and total protein content (43.47 +/- 3.85 micrograms/cm vs 21.95 +/- 2.5 micrograms/cm). Arginine did not influence the DNA content of the catheters or the rate of epithelialization of the skin defect. Peripheral blood lymphocyte responses to mitogenic and allogenic stimulation were greater in the arginine supplemented group. Serum insulin-like growth factor-1 levels were significantly elevated in the arginine group. CONCLUSIONS: The data suggest that arginine supplementation may improve wound healing and immune responses in the elderly.

Aged↗

Lipids and immune function.

Intravenous lipid emulsions as part of Total Parenteral Nutrition, are now standard in most centers. The most frequently used lipid formula contains predominantly long-chain triglycerides (LCT) of n-6 series . Controversy and concern exist about the immunosuppressive effects of this fuel source mainly based on experimental data because clinical studies are sparse. Some investigators have pointed out that this lipid emulsion impair monocyte, lymphocyte and neutrophil functions although these changes seem to be related to quantity and rate of lipid administration. A new lipid emulsion that contains 50% as medium chain triglycerides is available. The impact of this formula on immune function is unknown although some papers suggest that it produces less deleterious effects on immune response than the traditional lipid source. Prostaglandins and leukotrienes have numerous effects on immune functions and mediate many of the hemodynamic aspects of the metabolic response to injury. The use of n-3 fatty acids that produce less immunosuppressive eicosanoids have been studied in experimental model with hopeful results. Despite these conflicting data, almost all authors agree that there are no justification for withholding intravenous lipid therapy because they are safe and effective providing essential fatty acids with a high caloric content. Future studies are needed to define the precise composition of lipid emulsions that may vary in the different pathologic situations.

Fat Emulsions, Intravenous↗

Effect of glutamine on immune function in the surgical patient.

The beneficial effects of glutamine on immune function in vitro have been well described. Severely ill surgical patients undergo glutamine depletion and this has been implicated as a cause of immune dysfunction in vivo. With the introduction of the stable dipeptides of glutamine into total parenteral nutrition (TPN) regimens, the clinical effects of glutamine on the immune system have taken on an increased relevance and importance. In a randomized clinical trial, we have shown that glutamine-supplemented TPN increased the T cell mitogenic response in patients undergoing colorectal resection. This was not associated with an altered production of the pro-inflammatory cytokines interleukin-6 (IL-6) or tumor necrosis factor (TNF). In a subsequent clinical trial comparing glutamine-supplemented TPN with control TPN in patients with severe acute pancreatitis there was a similar modest enhancement of the T cell response in the glutamine-supplemented group. Although Il-6 and TNF production were again unchanged, there was a significant reduction in IL-8 production in the glutamine-supplemented group. Glutamine may exert its immunological effects by a direct action on the cells of the immune system. Possible indirect mechanisms by which glutamine may influence the immune system include the maintenance of gut barrier function, or the preservation of action of the antioxidant glutathione.

Glutamine↗

Effect of dietary cyclic nigerosylnigerose on intestinal immune functions in mice.

We examined the dietary effects of cyclic nigerosylnigerose (CNN), a dietary indigestible oligosaccharide with four D-glucopyranosyl residues linked by alternating alpha-(1-->3)- and alpha-(1-->6) glucosidic linkages, on the intestinal immune function of mice, and the effects were compared with those of alpha-(1-->3)-linked oligosaccharide (nigerooligosaccharides, NOS) or alpha-(1-->6)-linked oligosaccharide (isomaltooligosaccharides, IMO). BALB/c mice were fed with 1-5% CNN, 5% IMO, or 12.5% NOS for 4 weeks, and the intestinal mucosal immune responses were determined. In the 1-5% CNN fed groups, the amounts of IgA in feces increased significantly. In addition, IgA, transforming growth factor-beta1 (TGF-beta1), and interleukin-6 (IL-6) secretion by Peyer's patch (PP) cells were enhanced in CNN fed mice. In the 5% CNN group, pH in the cecum decreased, and the amounts of lactic acid and butyric acid increased. These findings were not observed in the NOS- or IMO-fed group of mice. They suggest that CNN supplementation changes the intestinal environment of microflora and indirectly enhances the immune function in the gut.

Animals↗