Nutrition, exercise and the immune system.
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Cytokines↗
Biomedical subjects
B K Pedersen
Publications and source records attributed to B K Pedersen.
Production of beta-chemokines in human immunodeficiency virus (HIV) infection: evidence that high levels of macrophage inflammatory protein-1beta are associated with a decreased risk of HIV disease progression.
Macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES production were measured by ELISA in whole blood that had been stimulated for 4.5 h with phytohemagglutinin. The blood was from 90 healthy human immunodeficiency virus (HIV)-negative controls and from 245 HIV-infected subjects who were followed for < or = 4.5 years. HIV-infected persons without AIDS had increased levels of MIP-1alpha, MIP-1beta, and RANTES (P < .01) compared with levels in controls. Subjects with AIDS, compared with controls, had decreased production levels of MIP-1beta (P < .0001) and similar levels of MIP-1alpha and RANTES. A high level of MIP-1beta production was associated with a decreased risk of progressing to AIDS or death, as determined by univariate analysis (P < .01) and adjusted for CD4 cell count and age (P = .07, P = .06, respectively). The findings suggest that the production level of beta-chemokine changes during HIV infection and that a high level of beta-chemokine production in peripheral blood lymphocytes may be associated with less rapid disease progression in HIV infection.
Acquired Immunodeficiency Syndrome↗
Effect of glutamine supplementation on changes in the immune system induced by repeated exercise.
UNLABELLED: The ability of lymphocytes to proliferate and generate lymphokine activated killer (LAK) cell activity in vitro is dependent on glutamine. In relation to intense exercise the lymphocyte concentration, the proliferative response, the natural killer and LAK cell activity, and the plasma glutamine concentration decline. It has been hypothesized that in relation to physical activity a lack of glutamine may temporarily affect the function of the immune system. PURPOSE: The purpose of this study was to examine the influence of glutamine supplementation on exercise-induced immune changes. METHODS: In a randomized cross-over placebo-controlled study, eight healthy male subjects performed three bouts of ergometer bicycle exercise lasting 60, 45, and 30 min at 75% of their VO2max separated by 2 h of rest. RESULTS: The arterial plasma glutamine concentration declined from 508 +/- 35 (pre-exercise) to 402 +/- 38 microM (2 h after the last exercise bout) in the placebo trial and was maintained above pre-exercise levels in the glutamine supplementation trial. The numbers of circulating lymphocytes and the phytohemagglutinin-stimulated lymphocyte proliferative response declined 2 h after, respectively, during each bout of exercise, whereas the LAK cell activity declined 2 h after the third bout. Glutamine supplementation in vivo, given in the described doses at the specific times, did not influence these changes. CONCLUSION: The present study does not appear to support the hypothesis that those aspects of postexercise immune changes studied are caused by decreased plasma glutamine concentrations.
Adult↗
The cytokine response to strenuous exercise.
Strenuous exercise is accompanied by an increase in circulating proinflammatory and inflammation responsive cytokines, having some similarities with the response to sepsis and trauma. The sequential release of tumour necrosis factor-alpha, interleukin (IL) 1 beta, IL-6, and IL-1 receptor antagonist (IL-1ra) in the blood is comparable to that observed in relation to bacterial diseases. Eccentric exercise is associated with an increase in serum IL-6 concentrations and is significantly correlated with the concentration of creatine kinase (CK) in the following days, whereas no changes are found after the concentric exercise; this demonstrates a close association between exercise-induced muscle damage and increased serum levels of IL-6. The time course of cytokine production, the close association with muscle damage, and the finding of mRNA-IL-6 in skeletal muscle biopsies after intense exercise all support the idea that during eccentric exercise myofibers are mechanically damaged and that this process stimulates the local production of inflammatory cytokines. It remains to be shown whether systemic endotoxemia during exercise is also a cause of elevated levels of cytokines in the plasma. The present review also discusses the possible roles of protein breakdown, delayed onset muscle soreness, and clinical implications of the acute-phase response following exercise.
Cytokines↗
N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise.
This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min "all-out" ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4(+), CD8(+), CD16(+), and CD19(+) cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 +/- 2,865 to 5,851 +/- 1,588 cpm (P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 +/- 3 to 38 +/- 4% and it decreased to 7 +/- 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16(+) cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.
Acetylcysteine↗
Influence of minor increases in plasma catecholamines on natural killer cell activity.
This study was designed to test the hypothesis that the modulations of the human immune system in relation to in vivo whole body hyperthermia may be ascribed to elevations in the plasma epinephrine and norepinephrine concentrations. In a single-blind, controlled, cross-over study, 8 healthy volunteers were selectively infused norepinephrine and epinephrine, respectively, for 1 h, in order to obtain twofold increases in the plasma concentrations of these hormones, thereby mimicking the increases seen during in vivo whole body hyperthermia. Epinephrine infusion increased baseline, interleukin-2 and interferon-alpha stimulated natural killer cell activity, and the percentage and concentration of cluster designation (CD)16+ cells, whereas the neutrophil and lymphocyte count or the CD3+, CD4+, CD8+, CD19+ and CD14+ cell subtypes were not influenced. Norepinephrine infusion did not cause any changes in these variables. It is concluded that epinephrine, but not norepinephrine, may be responsible for the hyperthermia-induced effects on natural killer cells.
Adult↗
Glutamine, exercise, and the immune system--is there a link?
Glutamine is known to be important for cells replicating in culture. It has been proposed that the decrease in plasma glutamine concentration in relation to catabolic conditions, including strenuous exercise, resulting in a lack of glutamine for cells of the immune system, is responsible for the transient postexercise immunosuppression. This review discusses the potential role of glutamine on the postexercise in-vitro changes in immune parameters. Furthermore, the value of glutamine as a nutritional supplement to athletes and the possible influence on these parameters is reviewed.
Animals↗
[Physical activity and cancer].
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Exercise↗
[Lowered number of CD4+cekks--reduced influx or increased loss?].
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CD4-Positive T-Lymphocytes↗
Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage.
1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.
Adult↗
Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Guérin.
Many aspects of the widely used bacillus Calmette-Guérin (BCG) vaccine against tuberculosis are still the subject of controversy. There is a huge variation in efficacy from one clinical trial to another and no relationship between vaccine-induced skin test conversion and subsequent protection. We have studied in vitro cell-mediated immune responses primed by BCG vaccination in 22 healthy Danish donors with different levels of in vitro purified protein derivative (PPD) reactivity before vaccination. The study demonstrated a markedly different development of reactivity to mycobacterial Ags depending on the prevaccination sensitivity to PPD. Previously sensitized donors mounted a potent and highly accelerated recall response within the first week of BCG vaccination. Nonsensitized donors, in contrast, exhibited a gradually increasing responsiveness to mycobacterial Ags, reaching maximal levels between day 56 and 365 postvaccination. The recognition of different classes of Ags were induced in a stepwise manner: culture filtrate Ags were recognized 1 wk postvaccination followed by cell wall, membrane, and the cytosolic Ag fraction. The T cell response primed by BCG vaccination was characterized as a CD4 response with a Th1-like cytokine pattern and substantial levels of Ag-specific cytotoxicity. The specificity of the T cell response generated was broad and directed to a range of culture filtrate Ag fractions. The study shows that BCG vaccination of previously nonsensitized donors can provide important data on potentially protective immune responses in humans and suggest a careful evaluation of prevaccination sensitivity when investigating vaccine-induced immunity.
Adolescent↗
Lymphocyte proliferation in response to exercise.
Lymphocyte proliferative responses are often used to evaluate the functional capacity of the immune system in response to exercise. Blood mononuclear cells (BMNC) are stimulated in vitro with polyclonal mitogens and the incorporation of 3H-thymidine into the DNA reflects cell proliferation. The BMNC are most often stimulated with either phytohaemagglutinin (PHA), poke weed mitogen (PWM), concanavalin A (Con-A), interleukin-2 (IL-2), or purified derivative of tuberculin (PPD). The literature concerning lymphocyte proliferation and exercise is reviewed with respect to the type and intensity of exercise, and also the effect of training status. The proliferative responses to exercise are highly heterogeneous, the most consistent finding being that PHA-stimulated cell responses decrease during exercise which may reflect a decreased fraction of CD3+ cells. In contrast, reduced, elevated or even unchanged lymphocyte proliferative response to PHA, PWM, Con-A, IL-2 and PPD have been demonstrated in the recovery period following exercise. Also variable responses are present in trained athletes compared to less fit subjects. Even though this may reflect that the time of 3H-thymidine incorporation into lymphocytes varies, we conclude that a functional evaluation of the immune system in response to exercise cannot be based solely upon measurements of lymphocyte proliferation.
Cell Division↗
Influence of Naloxone on the cellular immune response to head-up tilt in humans.
To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.
Adult↗
Hypoxemia increases serum interleukin-6 in humans.
Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood oxygen saturations were 78.6 (7.3)%, 82.4 (4.9)%, and 83.4 (5.3)% in the first, second, and third days at altitude, respectively. A symptom score of acute mountain sickness (AMS) revealed that the subjects had mostly light symptoms of AMS. Mean serum IL-6 increased from 1.36 (1.04) pg x ml(-1) at sea level to 3.10 (1.65), 4.71 (2.81), and 3,54 (2.17) pg x ml(-1) during the first three days at altitude, and to 9.96 (8.90) pg x ml(-1) on the fourth day at altitude (ANOVA p = 0.002). No changes occurred in serum concentrations of IL-1 beta, IL-1ra, TNF alpha, or CRP. The serum IL-6 were related to SaO2, (r = -0.45, p = 0.003), but not to heart rates or AMS scores. In conclusion, human serum concentrations of IL-6 increased during altitude hypoxia whereas the other proinflammatory cytokines remained unchanged. The major role of IL-6 during altitude hypoxia seem not to be mediation of inflammation, instead, the role of IL-6 could be to stimulate the erythropoiesis at altitude.
Adult↗
Clinical progression of HIV infection: role of NK cells.
The purpose of the study was to examine how immune parameters related to non-major histocompatibility complex (MHC) restricted cytotoxicity changed with respect to progression and duration of human immunodeficiency virus (HIV) infection. Forty-one HIV seropositive subjects with a known time for seroconversion were included. The major finding was that a low percentage and number of natural killer (NK) cells were found in the group who had a rapid progression to acquired immune deficiency syndrome (AIDS) (less than 70 months following seroconversion) compared with those progressing more slowly to AIDS (more than 70 months following seroconversion). Furthermore, a significant correlation was found between the number of months from seroconversion to the diagnosis of AIDS and percentages of CD16+ cells (rs = 0.811, P < 0.01), CD56+ cells (rs = 0.647, P < 0.05), and CD16+CD56+ cells (rs = 0.839, P < 0.01) as well as the concentration of CD16+CD56+ cells in the blood (rs = 0.699, P < 0.05) No differences were found in percentages and concentrations of NK cell subsets between subjects with a long history (more than 6 years) versus a short history (less than 6 years) of HIV infection without AIDS. Furthermore, no negative correlations were found between the concentration of any NK subsets and the number of months since seroconversion in HIV seropositive individuals without AIDS. The total concentration of CD16+, CD56+, and CD16+CD56+ cells was lower in the group of HIV seropositive subjects compared with HIV seronegative subjects (age and sex matched), and the concentration of CD16+ cells was lower in those with AIDS than in those without AIDS. In conclusion, low concentration of NK cells in the blood was associated with a more rapid disease progression, indicating that defective non-MHC restricted cytotoxicity may be associated with HIV disease progression.
Acquired Immunodeficiency Syndrome↗
Exercise-induced immunomodulation--possible roles of neuroendocrine and metabolic factors.
Acute muscular exercise induces an increased neutrophil count concomitant with recruitment of natural killer (NK), B and T cells to the blood as reflected by an elevation in the total lymphocyte count. Meanwhile, following intense exercise of long duration the lymphocyte count declines, non-MHC-restricted cytotoxicity is suppressed, but the neutrophil concentration increases. In relation to eccentric exercise involving muscle damage, the plasma concentrations of interleukin-1, interleukin-6 and the tumor necrosis factor are elevated. In this review we will propose a model based on the possible roles that stress hormones play a mediating the exercise- related immunological changes: adrenaline and to a lesser degree noradrenaline are responsible for the immediate effects of exercise on lymphocyte subpopulations and cytotoxic activities. The increase in catecholamines and growth hormone mediate the acute effects of exercise on neutrophils, whereas cortisol may be responsible for maintaining lymphopenia and neutrocytosis after exercise of long duration. Lastly, the role of beta-endorphin is less clear, but the cytokine response is closely related to muscle damage and stress hormones do not seem to be directly involved in the elevated cytokine level. Other possible mechanisms of exercise-induced immunomodulation may include the so-called glutamine hypothesis, which is based on the fact that skeletal muscle is an important source of glutamine production and that lymphocytes are dependent on glutamine for optimal growth. Furthermore, physiological changes during exercise, e.g. increased body temperature and decreased oxygen saturation may also in theory contribute to the exercise-induced immunological changes.
Catecholamines↗
Decreased short-term production of tumor necrosis factor-alpha and interleukin-1beta in human immunodeficiency virus-seropositive subjects.
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were measured by ELISA in 4.5-h, lipopolysaccharide-stimulated whole blood cultures of 347 human immunodeficiency virus type 1-infected patients and 107 healthy seronegative controls. The production of TNF-alpha was decreased in both AIDS and non-AIDS patients, whereas the production of IL-1beta was decreased in AIDS patients only. The production of TNF-alpha and IL-1beta was positively affected by the concentrations of CD14+ monocytes and CD8+ lymphocytes; however, in patients, the concentration of CD4+ lymphocytes and the presence of AIDS had a negative effect on cytokine production as determined by multiple linear regression analysis. It is concluded that low whole blood cytokine production is mainly caused by low numbers of cells, but a functional defect may also exist.
Acquired Immunodeficiency Syndrome↗
Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death: evidence from a cohort of 347 HIV-infected individuals.
OBJECTIVE: To examine changes in the distribution of CD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) lymphocytes in various stages of HIV infection and the effect of these changes on disease progression. DESIGN AND METHODS: Expression of CD45RA+ and CD45RO+ on CD4+ lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 300 HIV-infected individuals (median follow-up time, 2.90 years; range, 0.02-4.54 years) and in a group of 102 age- and sex-matched uninfected controls. Survival analysis was performed considering AIDS development and death as endpoints. RESULTS: The median CD4+CD45RA+/CD45RO+ ratio was 1.3 (25-75% quartiles, 0.9-2.4) in controls; it was increased to 1.8 (1.1-2.5) in 40 HIV-infected individuals with CD4+ cell counts > 500 x 10(6)/l (P < 0.05); it was similar at 1.4 (0.8-2.0) in 106 HIV-infected individuals with CD4+ cell counts of 200-500 x 10(6)/l; and it was decreased to 0.9 (0.5-1.4) in 154 HIV-infected individuals with CD4+ cell counts < 200 x 10(6)/l (P < 10[-6]). When fitted in a Cox model adjusting for the total number of CD4+ cells and age a lower concentration of CD4+CD45RA+ cells was associated with an increased risk of dying. The concentration of CD4+CD45RO+ cells was not significantly associated with AIDS or death in age- and CD4+ cell count-adjusted Cox models. CONCLUSIONS: This study confirms a selective loss of memory CD4+ cells early in HIV infection followed by increased loss of naive CD4+ cells in later stages of the infection. The loss of naive CD4+ cells seems to be important in the pathogenesis of terminal HIV infection.
CD4 Antigens↗