Effect of adrenergic blockade on lymphocyte cytokine production at rest and during exercise

2001 ◽  
Vol 281 (4) ◽  
pp. C1233-C1240 ◽  
Author(s):  
R. L. Starkie ◽  
J. Rolland ◽  
M. A. Febbraio

To examine the effect of exercise and adrenergic blockade on lymphocyte cytokine production, six men ingested either a placebo (control) or an α- (prazosin hydrochloride) and β-adrenoceptor antagonist (timolol malate) capsule (blockade, or BLK) 2 h before performing 19 ± 1 min of supine bicycle exercise at 78 ± 3% peak pulmonary uptake. Blood was collected before and after exercise, stimulated with phorbol 12-myristate 13-acetate and ionomycin, and surface stained for T (CD3+) and natural killer [NK (CD3−CD56+)] lymphocyte surface antigens. Cells were permeabilized, stained for the intracellular cytokines interleukin (IL)-2 and interferon (IFN)-γ, and analyzed using flow cytometry. BLK had no effect on the resting concentration of stimulated cytokine-positive T and NK lymphocytes or the amount of cytokine they were producing. Exercise resulted in an increase ( P< 0.05) in the concentration of stimulated T and NK lymphocytes producing cytokines in the circulation, but these cells produced less ( P < 0.05) cytokine post- compared with preexercise. BLK attenuated ( P < 0.05) the elevation in the concentration of lymphocytes producing cytokines during exercise; however, BLK did not affect the amount of IL-2 and IFN-γ produced. These results suggest that adrenergic stimulation contributes to the exercise-induced increase in the concentration of lymphocytes in the circulation; however, it does not appear to be responsible for the exercise-induced suppression in cytokine production.

2005 ◽  
Vol 98 (2) ◽  
pp. 565-571 ◽  
Author(s):  
G. I. Lancaster ◽  
Q. Khan ◽  
P. T. Drysdale ◽  
F. Wallace ◽  
A. E. Jeukendrup ◽  
...  

The present study was undertaken to examine the role of the exercise-induced stress hormone response on the regulation of type 1 and type 2 T lymphocyte intracellular cytokine production. Subjects performed 2.5 h of cycling exercise at 65% maximal O2 uptake while ingesting a 6.4% carbohydrate (CHO) solution, 12.8% CHO solution, or a placebo. Peripheral whole blood samples were stimulated and stained for T lymphocyte surface antigens (CD4 and CD8). Cells were then permeabilized, stained for intracellular cytokines, and analyzed using flow cytometry. Exercise resulted in a decrease ( P < 0.05) in the number and percentage of IFN-γ positive CD4+ and CD8+ T lymphocytes. These stimulated cells produced less IFN-γ immediately postexercise ( P < 0.05) and 2-h postexercise ( P < 0.05) compared with preexercise. However, CHO ingestion, which attenuated the exercise-induced stress hormone response compared with placebo ( P < 0.05), prevented both the decrease in the number and percentage of IFN-γ-positive CD4+ and CD8+ T lymphocytes and the suppression of IFN-γ production from stimulated CD4+ and CD8+ T lymphocytes. There was no effect of exercise on the number of, or cytokine production from, IL-4-positive CD4+ or CD8+ T lymphocytes. These data provide support for the role of exercise-induced elevations in stress hormones in the regulation of type 1 T lymphocyte cytokine production and distribution.


1995 ◽  
Vol 268 (5) ◽  
pp. E910-E916 ◽  
Author(s):  
L. S. Lamont ◽  
A. J. McCullough ◽  
S. C. Kalhan

The purpose of this study was to assess the interaction between beta-blockade and exercise on amino acid kinetics. This was a three-way crossover experiment using beta 1-blockade, beta 1,beta 2-blockade, and a placebo control. Three 6-h L-[1-13C]leucine and L-[alpha-15N]lysine infusions were performed. The first 3 h established an isotopic steady state, and 1 h of exercise (approximately 50% of maximal O2 consumption) and 2 h of recovery followed. Plasma glucose decreased with exercise during all trials (P < 0.0001). During beta 1- and beta 1,beta 2-blockade, plasma free fatty acids were reduced during rest and exercise (P < 0.001). Leucine and lysine rates of appearance were unaffected by beta-blockade during rest but were decreased with placebo exercise. Leucine oxidation increased with beta-blockade (P < 0.01) and exercise (P < 0.001). There was a statistical interaction between both treatments (P < 0.004). In conclusion, leucine oxidation increased with exercise, further increased with beta 1-blockade, and was additionally heightened with beta 1,beta 2-blockade. This cumulative response indicates that leucine oxidation was regulated through beta 1- and beta 2-receptors.


1975 ◽  
Vol 229 (4) ◽  
pp. 977-982 ◽  
Author(s):  
MJ Zinner ◽  
JC Kerr ◽  
DG Reynolds

The effects of adrenergic stimulation and blockade on the gastric circulation were studied in anesthetized dogs. Blood flow through the right and left gastric artery was measured electromagnetically. Norepinephrine and isoproterenol were injected intra-arterially and intravenously before and after alpha- and beta-adrenergic blockade. Isoproterenol caused vasodilation of both right and left gastric circulations and this effect was attenuated by beta blockade. Epinephrine and norepinephrine induced constriction followed by dilation in both circulations. The constrictor components were attenuated or abolished by alpha-adrenergic blockade and the dilator components were attenuated by beta-adrenergic blockade. The right and left gastric vascular beds demonstrated quantitatively different responses to the same dose of each adrenergic amine. The left gastric circulation had a greater vasodilator response than did the right gastric circulation. These data support the classical concepts that epinephrine and norepinephrine are "mixed" adrenergic agonists and isoproterenol is a "pure" beta-adrenerigic agonist. The data further suggest that there is a differential in beta-adrenergic receptor distribution with the left gastric vasculature demonstrating greater dilator responses than the right.


2011 ◽  
pp. 599-609
Author(s):  
I. FALCÃO-PIRES ◽  
A. P. FONTES-SOUSA ◽  
L. LOPES-CONCEIÇÃO ◽  
C. BRÁS-SILVA ◽  
A. F. LEITE-MOREIRA

The acute effects of β-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10-10-10-5 M), a non-selective β-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (β1-adrenoceptor antagonist), ICI-118551 (β2-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10-5 M). In the control group, isoprenaline increased resting muscle length up to 1.017±0.006 L/Lmax. Correction of resting muscle length to its initial value resulted in a 28.5±3.1 % decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive length-tension relation. These effects were modulated by β1- and β2-adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that β-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased.


Author(s):  
Sarah Skinner ◽  
Elie Nader ◽  
Emeric Stauffer ◽  
Mélanie Robert ◽  
Camille Boisson ◽  
...  

BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte concentrations and cytokine profiles. METHODS: The study was conducted during the Ultra-Trail du Mont Blanc® ultra-marathon running event, and included 11 runners who completed the 40 km trail run and 12 runners who completed the 171 km ultra-trail. Blood samples were taken before and after the races. RESULTS: Leukocyte concentrations significantly increased after both races. Circulating levels of IL-6, IL-1β, MCP-1, and IFN-γ were significantly higher after the longer race compared to the shorter race. Furthermore, while both races resulted in significant increases in IL-6 and IL-8, only the longer race resulted in significant increases in MIP-1β, IL-7, IL-17a, and IL-4. CONCLUSIONS: These results illustrate that a 171 km ultra-trail race results in greater modulations in cytokine profiles than a traditional trail race.


Author(s):  
Mohammad Reza. Shiran ◽  
Davar Amani ◽  
Abolghasem Ajami ◽  
Mahshad Jalalpourroodsari ◽  
Maghsoud Khalizadeh ◽  
...  

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.


2011 ◽  
Vol 300 (6) ◽  
pp. R1443-R1451 ◽  
Author(s):  
Lauren G. MacNeil ◽  
Steven K. Baker ◽  
Ivan Stevic ◽  
Mark A. Tarnopolsky

17β-estradiol (E2) attenuates exercise-induced muscle damage and inflammation in some models. Eighteen men completed 150 eccentric contractions after random assignment to placebo (Control group) or E2 supplementation (Experimental group). Muscle biopsies and blood samples were collected at baseline, following 8-day supplementation and 3 h and 48 h after exercise. Blood samples were analyzed for sex hormone concentration, creatine kinase (CK) activity and total antioxidant capacity. The mRNA content of genes involved in lipid and cholesterol homeostasis [forkhead box O1 (FOXO1), caveolin 1, and sterol regulatory element binding protein-2 (SREBP2)] and antioxidant defense (SOD1 and -2) were measured by RT-PCR. Immunohistochemistry was used to quantify muscle neutrophil (myeloperoxidase) and macrophage (CD68) content. Serum E2 concentration increased 2.5-fold with supplementation ( P < 0.001), attenuating neutrophil infiltration at 3 h ( P < 0.05) and 48 h ( P < 0.001), and the induction of SOD1 at 48 h ( P = 0.02). Macrophage density at 48 h ( P < 0.05) and SOD2 mRNA at 3 h ( P = 0.01) increased but were not affected by E2. Serum CK activity was higher at 48 h for both groups ( P < 0.05). FOXO1, caveolin 1 and SREBP2 expression were 2.8-fold ( P < 0.05), 1.4-fold ( P < 0.05), and 1.5-fold ( P < 0.001) and higher at 3 h after exercise with no effect of E2. This suggests that E2 attenuates neutrophil infiltration; however, the mechanism does not appear to be lesser oxidative stress or membrane damage and may indicate lesser neutrophil/endothelial interaction.


2005 ◽  
Vol 288 (6) ◽  
pp. G1195-G1198 ◽  
Author(s):  
Shi Liu ◽  
Lijie Wang ◽  
J. D. Z. Chen

Gastric electrical stimulation (GES) has been shown to alter motor and sensory functions of the stomach. However, its effects on other organs of the gut have rarely been investigated. The study was performed in 12 dogs implanted with two pairs of electrodes, one on the serosa of the stomach and the other on the colon. The study was composed of two experiments. Experiment 1 was designed to study the effects of GES on rectal tone and compliance in nine dogs compared with colonic electrical stimulation (CES). Rectal tone and compliance were assessed before and after GES or CES. Experiment 2 was performed to study the involvement of sympathetic pathway in 8 of the 12 dogs. The rectal tone was recorded for 30–40 min at baseline and 20 min after intravenous guanethidine. GES or CES was given for 20 min 20 min after the initiation of the infusion. It was found that both GES and CES reduced rectal tone with comparable potency. Rectal compliance was altered neither with GES, nor with CES. The inhibitory effect of GES but not CES on rectal tone was abolished by an adrenergic blockade, guanethidine. GES inhibited rectal tone with a comparable potency with CES but did not alter rectal compliance. The inhibitory effect of GES on rectal tone is mediated by the sympathetic pathway. It should be noted that electrical stimulation of one organ of the gut may have a beneficial or adverse effect on another organ of the gut.


1976 ◽  
Vol 41 (3) ◽  
pp. 383-387 ◽  
Author(s):  
D. L. Eckberg ◽  
F. M. Abboud ◽  
A. L. Mark

Carotid baroreceptors were stimulated with graded neck suction in supine and standing volunteers, before and after autonomic blockade, to determine the influence of posture on baroreflex responsiveness. Propranolol significantly augmented baroreflex pulse interval prolongation in the supine position. Upright posture did not modify baroreflex pulse interval responses prior to propranolol, but significantly augmented responses after propranolol. The results suggest that standing enhances baroreflex sensitivity, but that under normal circumstances, this effect is masked by beta-adrenergic stimulation. Augmentation of baroreflex pulse interval prolongation in the supine and standing positions by propranolol may contribute to the effectiveness of this drug in angina pectoris and labile hypertension.


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