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B K Pedersen

Publications and source records attributed to B K Pedersen.

At least 199 records · Page 11Linked to original sources

Evidence that the effect of physical exercise on NK cell activity is mediated by epinephrine.

The present study was designed to test the hypothesis that the changes in natural killer (NK) cell activity in response to physical exercise were mediated by increased epinephrine concentrations. Eight healthy volunteers 1) exercised on a bicycle ergometer (60 min, 75% of maximal O2 uptake) and 2) on a later day were given epinephrine as an intravenous infusion to obtain plasma epinephrine concentrations comparable with those seen during exercise. Blood samples were collected in the basal state, during the last minutes of exercise or epinephrine infusion, and 2 h later. The NK cell activity (lysis/fixed number of mononuclear cells) increased during exercise and epinephrine infusion and dropped below basal levels 2 h afterward. The increased NK cell activity during exercise and the epinephrine infusion resulted from an increased concentration of NK (CD16+) cells in the peripheral blood. On the other hand, the decreased NK cell activity demonstrated 2 h after exercise and epinephrine infusion did not simply reflect preferential removal of NK cells from the blood, because the proportion of CD16+ cells was normalized. On the basis of the finding that indomethacin abolished the suppressed NK cell activity in vitro and the demonstration of a twofold increase in the proportion of monocytes (CD14+ cells) 2 h after exercise and epinephrine infusion, we suggest that, after stress, prostaglandins released by monocytes are responsible for downregulation of NK cell function. Our findings support the hypothesis that increased plasma epinephrine during physical stress causes a redistribution of mononuclear subpopulations that results in altered function of NK cells.

Adult↗

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines.

In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.

Adult↗

Effects of in vitro hyperthermia on the proliferative response of blood mononuclear cell subsets, and detection of interleukins 1 and 6, tumour necrosis factor-alpha and interferon-gamma.

The role of endogenously mediated fever and exogenous hyperthermia as modulators of immune functions remains poorly understood. It is known that fever is mediated by several cytokines, including interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and the interferons. The present communication examines the effect of exogenous hyperthermia on the detection of these cytokines and shows the suppressive effect of elevated temperature (39 degrees) on the amount of IL-1 beta, IL-6 and IFN-gamma (P less than 0.001) but not on IL-1 alpha and TNF-alpha concentrations. It is suggested that a negative feedback mechanism exists between temperature and the production of some of the molecules involved in the mediation of fever. It is known that hyperthermia increases the proliferative response of lymphocytes. We found a twofold increase in [3H]thymidine incorporation at 39 degrees compared to 37 degrees. The distribution of cells expressing CD3, CD4, CD8, CD14, CD16, CD19 and CD25 markers was the same at 37 degrees and 39 degrees.

Antigens, CD↗

Immune parameters in male atheletes after a lacto-ovo vegetarian diet and a mixed Western diet.

The influence of a lacto-ovo vegetarian diet versus a meat-rich Western diet on in vitro measures of immune function was studied in eight male endurance athletes. Subjects consumed two different diets for 2 x 6 wk, separated by 4 wk on an ad libitum diet, in a cross-over design. Both diets consisted of 57 energy % (E%) carbohydrates, 14 E% protein and 29 E% fat. One diet was a mixed meat-rich diet (M) prepared with 69% animal protein sources, whereas the other diet (V) was a lacto-ovo vegetarian diet prepared with 82% vegetable protein sources. Blood for determination of leukocyte subpopulations and in vitro function was collected at the end of each diet period 36 h after the last training bout. Fiber content and P/S ratio of fatty acids were twice as high on the V diet as on the M diet. Training volume was similar on the two diets, and maximal aerobic capacity did not change during diet periods. The number of CD3+ (pan T-cells), CD8+ (mainly T suppressor cells), CD4+ (mainly T helper cells), CD16+ (natural killer cells), and CD14+ (monocytes) was similar after the two different diets. Similarly, proliferations of mononuclear cells after stimulation with interleukin-2 (IL-2), phytohemagglutinin, and purified derivative of tuberculin (PPD), as well as activity of natural killer cells in the unstimulated state and after stimulation with IL-2, indomethacin, and interferon-alpha (IFN-alpha), were identical after the two diet periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Indomethacin in vitro and in vivo abolishes post-exercise suppression of natural killer cell activity in peripheral blood.

The present study was designed to explain the mechanism of the post-exercise down-regulation of human natural killer (NK) cell activity recently described by us. Fifteen young, healthy volunteers underwent 60 min of bicycle exercise at 75% of maximal oxygen uptake (VO2max). Six of the volunteers were exercised twice with an interval of at least one month. At the second exercise test they received oral indomethacin. Blood samples were collected before and during the last minutes of exercise as well as 2 h and 24 h after work. The NK cell activity (lysis fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. During bicycle exercise the percentage of NK cells (CD16+ cells) of mononuclear cells increased significantly but returned to normal within 2 h after exercise. Two hours after exercise, however, increased monocyte cell count and neutrophils were found. The in vitro release of prostaglandin E2 from mononuclear cells was increased. Furthermore, the neutrophil chemiluminescence response was also increased in the 2 h post-exercise period; this response is associated with prostaglandin E2 production by neutrophils. Indomethacin, whether administered in vivo or in vitro, fully restored the suppressed post-exercise NK cell activity. Finally, the NK cell activity of monocyte depleted mononuclear cells did not decrease below basal levels after exercise. These findings strongly indicate that prostaglandins released from monocytes and neutrophils are involved in the post-exercise down-regulation of NK cells.

Adult↗

Effects of isoprinosine treatment of HIV-positive patients on blood mononuclear cell subsets, NK- and T-cell function, tumour necrosis factor, and interleukins 1, 2, and 6.

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment. Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-alpha), IL-2, or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) alpha or beta, IL-2, IL-6, or tumour necrosis factor (TNF).

Adult↗

Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.

Acute Disease↗

Inhibition of human natural killer cell activity by Legionella pneumophila protease.

The present study was undertaken to define the effect of Legionella pneumophila protease on natural killer (NK) cell function in vitro. Lysis of target cells by human NK cells was determined using a 51Cr-release assay. The protease inhibited the NK cell cytolytic activity in a concentration- and time-dependent manner. The inhibitory effect of the protease was not affected by alpha interferon or interleukin 2. Legionella pneumophila protease partly inhibited the binding of effector cells to target cells as studied in a single cell agarose assay of monocyte-depleted cell populations. This effect of the protease on the binding of NK cells to target cells could interfere with the previously described enhanced NK cell activity induced by Legionella pneumophila. We could demonstrate in vitro inhibition of NK cell activity by Legionella pneumophila protease at very low concentrations, suggesting a possible relevance of this mechanism in the pathogenesis of Legionnaires' disease.

Cytotoxicity, Immunologic↗

Natural killer cell activity in peripheral blood of highly trained and untrained persons.

Natural killer (NK) cell activity and concentration of CD16+ cells (NK cells) and CD20+ cells (monocytes) in peripheral blood were measured in highly trained racing cyclists and in age- and sex-matched untrained controls. Median NK cell activity was 38.1% (range 20.0%-57.1%) in trained vs 30.3% (range 19.7%-43.1%) in untrained (P = 0.008). Median %CD16+ cells was 17% (range 7%-33%) in trained vs 11% (3%-29%) in untrained (P = 0.007). Indomethacin in vitro enhanced the NK cell activity in both groups. There was, however, no significant difference between the NK cell activity in trained and untrained after exposure to indomethacin in vitro. Indomethacin-enhanced NK cell activity was 45.9% (range 24.4%-67.5%) in trained and 40.0% (range 23.9%-68.5%) in untrained (P = 0.138). Mean %CD14+ cells was 8.3% (range 2%-15%) in trained vs 3.8% (2%-8%) in untrained (P less than 0.0001). The increased NK cell function thus demonstrated in highly trained persons might result in better resistance against infectious disease.

Adult↗

Effect of physical exercise on blood mononuclear cell subpopulations and in vitro proliferative responses.

The present study was designed to examine the effect of physical exercise on subsets and proliferative responses of blood mononuclear cells. Sixteen young, healthy volunteers underwent 60 min of bicycle exercise at 75% of maximal oxygen uptake (VO2max). After an interval of at least 1 week, six of the subjects underwent a 60-min back muscle training period at up to 30% of VO2max. Blood samples were collected before and during the last minutes of exercise, as well as 2 and 24 h later. Blood mononuclear cell (BMNC) subpopulations were determined and the proliferative responses after incubation with phytohaemagglutinin (PHA) or purified derivative of tuberculin (PPD), were quantified by [3H]thymidine incorporation. During bicycle exercise the relative blood concentration of T cells (CD3+ cells) declined, mainly due to a fall in T helper cells (CD4+ cells). The natural killer (NK) cell subset (CD16+ cells) increased during work, but reverted after; the monocytes (CD14+ cells) increased 2 h after work, whereas the B-cell subset (CD20+ cells) did not change. BMNC subsets were not significantly changed by back muscle exercise. The PHA-induced proliferative response decreased during bicycle exercise, whereas the PPD-induced response did not change. No significant changes occurred during back muscle exercise. Investigation of subgroups after incubation with [3H]thymidine showed that the proliferative response per CD4+ cell did not change in relation to exercise, but the contribution of the CD4+ subgroup to proliferation declined during bicycle exercise due to the decreased proportion of CD4+ cells. The suppression of the PHA response during bicycle exercise can be explained in part by a relative fall in CD4+ cells. The pool sizes of BMNC subfraction may be elicited by increased catecholamine and cortisol levels.

Adult↗

Characterization of the natural killer cell activity in Hashimoto's and Graves' diseases.

Natural killer (NK) cell activity and blood mononuclear cell subpopulations were characterized in patients with Hashimoto's thyroiditis (n = 11), Graves' disease (n = 20), non-toxic goitre (n = 10) and in normal controls (n = 22). NK cell activity against K 562 target cells and the capability of IFN-alpha, Il-2, and indomethacin to enhance NK cell activity in vitro did not differ significantly between the groups. The percentages of large granular lymphocytes, CD5+, CD4+, CD8+ and CD16+ cells were normal in patients with non-toxic goitre, Hashimoto's and Graves' diseases. There was no correlation between NK cell activities and TgAb, MAb and TSAb. Although NK cell activity is suppressed in several autoimmune diseases, NK cell function is normal in patients with autoimmune thyroid disorders.

Adult↗

Suppressed natural killer cell activity in patients with euthyroid Graves' ophthalmopathy.

The purpose of the present study was to determine whether patients with euthyroid Graves' exophthalmopathy have an impaired NK cell function compared to patients with Graves' hyperthyroidism and healthy controls. The NK cell activity measured against K562 target cells was significantly suppressed (p less than 0.01) in patients with euthyroid Graves' ophthalmopathy, whereas the NK cell activity of patients with Graves' hyperthyroidism was not. Although interferon-alpha, interleukin-2 and indomethacin significantly enhanced (p less than 0.01) the NK cell activity in all three groups, none of these agents fully restored the defective NK cell activity in euthyroid Graves' ophthalmopathy. The concentrations in the blood of large granular lymphocytes and CD16 positive cells did not differ between the three groups, furthermore an immunosuppressive serum factor was not detected. The number of effector/target cell conjugates did not differ between patients and controls, whereas the interferon-alpha induced production of a soluble natural killer cytotoxic factor (NKCF) with specificity for NK sensitive target cells was suppressed in patients with Graves' euthyroid ophthalmopathy. We conclude that one of the mechanisms underlying the defective NK cell activity in patients with euthyroid ophthalmopathy may be an impairment of the release of NKCF from the NK cells.

Adolescent↗

Mechanisms of B-lymphocyte suppression induced by acute physical exercise.

Blood mononuclear cells from 20 healthy untrained volunteers were isolated before, during, 2 hr and 24 hr after bicycle exercise at 80% of VO2 max for 1 hr. A reverse plaque forming cell assay was used to investigate B-lymphocyte function. Stimulation with pokeweed mitogen, recombinant interleukin 2 and Epstein-Barr virus resulted in significant decreases in numbers of IgG-, IgM- and IgA-secreting blood cells during as well as 2 hr after exercise, with reversal to pre-exercise values 24 hr later. During and after physical activity we found an unchanged concentration of CD20-positive B lymphocytes suggesting that the suppression of immunoglobulin secreting cells was not due to changes in numbers of B lymphocytes. A decline in CD4/CD8 ratio was measured only during exercise with normalization after exercise. Therefore the B-lymphocyte suppression, most pronounced 2 hr after exercise, was presumably not due to changes in T lymphocytes also indicated in the experiments using EBV-stimulated cultures since EBV acts directly on B lymphocytes. 2 hr after physical activity an increased level of CD14-positive monocytes were observed and the monocytes expressed higher levels of surface HLA-DR during as well as 2 hr after exercise. Addition of indomethacin caused an increased response only in the IL-2 stimulated cultures, suggesting that IL-2-sensitive activated B lymphocytes are downregulated by prostaglandins. Purified B lymphocytes produced plaques only after EBV-stimulation, and in these cultures no exercise-induced suppression was found, likewise suggesting an inhibitory effect of the activated monocytes.

Adult↗

Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity.

In a randomized study of patients undergoing major elective abdominal surgery, 12 received i.v. ranitidine (50 mg every 6 hours for 72 hours from the skin incision) and 12 had no ranitidine. Cell-mediated immunity was assessed pre- and postoperatively by skin testing with seven common delayed type hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper/inducer-T cells, suppressor/cytotoxic-T cells, Pan-T cells and NK-cells) were counted by flow-cytometry. Perioperative ranitidine diminished the expected postoperative reduction in DTH responses (p less than 0.0001), as well as in spontaneous NK-cell activity (p less than 0.03) and in vitro IL-2 stimulated NK-cell activity (p less than 0.02). Postoperative decrease in helper/inducer-T cell numbers was not significantly lessened (p = 0.07), and ranitidine did not influence the levels of suppressor-T cells. PHA and PPD responses in peripheral blood mononuclear cells were unaltered. The results may suggest potential benefit from ranitidine as regards postoperative infectious complications and recurrence of malignancy.

Abdomen↗

Modulation of natural killer cell activity in peripheral blood by physical exercise.

The present study was designed to examine the effect of physical exercise on human natural killer (NK) cells. Six healthy volunteers underwent two different acute physical exercise tests with an interval of at least 1 week: (1) 60 min bicycle exercise at 80% of maximal oxygen uptake (VO2max) and (2) 60 min back-muscle training at up to 29% of VO2max; blood samples were collected before and during the last few minutes of exercise, as well as 2 h and 24 h afterwards. The NK cell activity (lysis/fixed number of mononuclear cells) increased during bicycle exercise, dropped to a minimum 2 h later and returned to pre-exercise levels within 24 h. Back-muscle exercise did not significantly influence NK cell activity. Plasma levels of adrenaline, noradrenaline, and cortisol were elevated during bicycling, but not during back-muscle exercise, indicating that exercise intensity is a determinant of NK cell activity. During bicycle exercise the NK cell subset (CD16- cells) of mononuclear cells increased significantly. Furthermore an improved interleukin 2 (IL-2) boosting of the NK cell activity was found during work as compared to IFN-alpha and indomethacin-enhanced NK cell activity. These results indicate that NK cells with a high IL-2 response capacity are recruited to the peripheral blood during exercise. The decreased NK cell activity demonstrated 2 h after work was probably not due to fluctuations in size of the NK cell pool, since the proportion of CD16+ cells was normal. The finding that indomethacin fully restored the suppressed NK cell activity in vitro and the demonstration of a twofold increase in monocyte (CD20+ cells) proportions 2 h after work, strongly indicate that prostaglandins released by monocytes during the heavy physical exercise are responsible for the down-regulation of the NK cells.

Adult↗

Cell-mediated immunity to Plasmodium falciparum infection: evidence against the involvement of cytotoxic lymphocytes.

Blood mononuclear cells (PBMC) recognizing soluble malaria antigens (SPag) are present in the peripheral blood of individuals clinically immune to malaria, and they proliferate after exposure to such antigens. To test whether these cells have effector activity against Plasmodium falciparum, we stimulated PBMC from malaria-immune donors by SPag and purified protein derivative (PPD) in culture for 7 days. The PBMC were then co-incubated with P. falciparum for 48 h, and parasitaemia was determined by microscopy. Parasite growth was only significantly impaired after incubation with PBMC stimulated by either SPag or PPD in the presence of immune serum. Studies on subpopulations of PBMC indicated that the inhibitory cells resided among the adherent cell fraction. Furthermore we tested PBMC for cytotoxic activity against P. falciparum-infected autologous or heterologous erythrocytes. Experiments were done both in the absence and the presence of immune serum. Neither fresh PBMC nor PBMC activated by SPag or PPD for 7 days prior to assay were cytotoxic, indicating that cytotoxic T cells, natural killer (NK) cells, and K cells did not possess cytotoxic activity directed against parasitized erythrocytes. These data support the hypothesis that activated monocytes are the most important effector cells in the peripheral blood of malaria immune individuals.

Animals↗

The in vivo effect of triethylphosphine gold (auranofin), sodium aurothiomalate and azathioprine on lymphocyte subsets of patients with rheumatoid arthritis.

The percentages of CD5+ (pan T), CD8+ (mainly T suppressor) and CD4+ (mainly T helper) cells were studied in 80 patients with rheumatoid arthritis (RA), grouped according to medication into four groups: 1) controls, not receiving remission-inducing therapy, 2) patients on oral gold (triethylphosphine gold, auranofin), 3) patients on parenteral gold (sodium aurothiomalate) and 4) patients on azathioprine. The total number of lymphocytes was not influenced by treatment with auranofin or sodium aurothiomalate, while the number of lymphocytes was depressed in the azathioprine-treated group (P less than 0.01). Neither treatment with azathioprine or parenteral gold, nor treatment with azathioprine influenced the CD4+/CD8+ ratio.

Adolescent↗

Bambuterol: clinical effects of three doses of bambuterol once daily in asthmatic patients.

Twenty-two asthmatics received bambuterol solution, a terbutaline pro-drug, once every evening. The following doses were each given orally for 7 days in a double-blind cross-over study: 0.185, 0.270 and 0.400 mg/kg. Bambuterol 0.270 mg/kg was preferable regarding clinical effects and side effects. The plasma concentration of generated terbutaline showed a slow linear decrease at all doses. Tests of two methods for objective measurements of tremor in five patients did not add any new data compared with the subjective recordings.

Adult↗