N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise

1998 ◽  
Vol 275 (4) ◽  
pp. R1227-R1231
Author(s):  
H. B. Nielsen ◽  
N. H. Secher ◽  
M. Kappel ◽  
B. K. Pedersen

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.

1994 ◽  
Vol 10 (3) ◽  
pp. 149-154 ◽  
Author(s):  
Andrew Campbell ◽  
Nachman Brautbar ◽  
Aristo Vojdani

We have previously shown that natural killer (NK) cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities (Vojdani et al, 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel. This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone. Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al, 1994).


Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.


Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 344-348 ◽  
Author(s):  
A Kist ◽  
AD Ho ◽  
U Rath ◽  
B Wiedenmann ◽  
A Bauer ◽  
...  

Abstract Tumor necrosis factor (TNF), a protein predominantly produced by activated macrophages/monocytes, is presently available in recombinant, purified form for clinical trials. Intensive studies in many laboratories have shown that besides the tumorcytotoxic effects, TNF acts on a large array of different cells and has potent immunomodulatory activities. In a clinical phase I study, some immunologic functional parameters of blood cells from patients who received 24-hour infusions of recombinant human TNF (rhTNF) were analyzed. Natural killer (NK) cell activity, TNF production, interleukin-1 (IL-1) production and mitogen-induced proliferation were measured either in whole blood samples or in cultures of peripheral mononuclear leukocytes of the patients directly before and after rhTNF infusion. NK cell activity, TNF and IL-1 production capacity and proliferative responses to concanavalin A (Con A) were significantly reduced after rhTNF application. We conclude from these observations that rhTNF in vivo acts directly or indirectly on NK cells and monocytes by either inactivating their functional capacity or by absorbing the relevant cells to the endothelial cell layer, thus removing them from circulation.


1999 ◽  
Vol 276 (5) ◽  
pp. R1496-R1505
Author(s):  
Shawn G. Rhind ◽  
Greg A. Gannon ◽  
Masatoshi Suzui ◽  
Roy J. Shephard ◽  
Pang N. Shek

Natural killer (NK) cells are important in combating viral infections and cancer. NK cytolytic activity (NKCA) is often depressed during recovery from strenuous exercise. Lymphocyte subset redistribution and/or inhibition of NK cells via soluble mediators, such as prostaglandin (PG) E2 and cortisol, are suggested as mechanisms. Ten untrained (peak O2 consumption = 44.0 ± 3.5 ml ⋅ kg−1 ⋅ min−1) men completed at 2-wk intervals a resting control session and three randomized double-blind exercise trials after the oral administration of a placebo, the PG inhibitor indomethacin (75 mg/day for 5 days), or naltrexone (reported elsewhere). Circulating CD3−CD16+/56+NK cell counts, PGE2, cortisol, and NKCA were measured before, at 0.5-h intervals during, and at 2 and 24 h after a 2-h bout of cycle ergometer exercise (65% peak O2 consumption). During placebo and indomethacin conditions, exercise induced significant ( P < 0.0001) elevations of NKCA (>100%) and circulating NK cell counts (>350%) compared with corresponding control values. With placebo treatment, total NKCA was suppressed (28%; P < 0.05) 2 h after exercise, and a postexercise elevation (36%; P = 0.02) of circulating PGE2 was negatively correlated ( r = 0.475, P = 0.03) with K-562 tumor cell lysis. NK counts were unchanged in the postexercise period, but at this stage CD14+ monocyte numbers were elevated ( P < 0.0001). Indomethacin treatment eliminated the postexercise increase in PGE2 concentration and completely reversed the suppression of total and per CD16+56+NKCA 2 h after exercise. These data support the hypothesis that the postexercise reduction in NKCA reflects changes in circulating PGE2 rather than a differential lymphocyte redistribution.


Author(s):  
Su-Jin Jung ◽  
Hui-Yeon Jang ◽  
Eun-Soo Jung ◽  
Soon-Ok Noh ◽  
Sang-Wook Shin ◽  
...  

Objective: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. Methods: Subjects (3x103 &le; peripheral blood leukocyte levels &lt; 8x103 cells/&mu;l) who met the inclusion criteria were recruited for this study. Enrolled subjects (n=120) were randomly assigned to either the PTE group (n=60) who were given 2.5 g/day of PTE (as Porphyra tenera extract) in capsule form or the placebo group (n=60) who were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed by measuring natural killer cell (NK-cell) activity, cytokines, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. Results: Compared to baseline, NK cell activity (%) increased for all effector cell to target cell ratios in the PTE group after 8 weeks, but there were no changes in the placebo group (p&lt;0.1). Subgroup analysis of 101 subjects without an URI revealed that NK-cell activity in the PTE group tended to be increased for all E:T ratios (E:T=12.5:1 p=0.068; E:T=25:1 p=0.036; E:T=50:1 p=0.081) compared to the placebo group. There was a significant difference between these two groups for the E:T=25:1 ratio, which increased from 20.3&plusmn;12.0% at baseline to 23.2&plusmn;12.4% after 8 weeks in the PTE group (p=0.036). There was no significant difference in levels of cytokines between these two groups. Conclusions: PTE supplementation appears to enhance immune function by improving NK-cell activity without adverse effects in healthy adults.


Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  

Abstract Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.


Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 344-348
Author(s):  
A Kist ◽  
AD Ho ◽  
U Rath ◽  
B Wiedenmann ◽  
A Bauer ◽  
...  

Tumor necrosis factor (TNF), a protein predominantly produced by activated macrophages/monocytes, is presently available in recombinant, purified form for clinical trials. Intensive studies in many laboratories have shown that besides the tumorcytotoxic effects, TNF acts on a large array of different cells and has potent immunomodulatory activities. In a clinical phase I study, some immunologic functional parameters of blood cells from patients who received 24-hour infusions of recombinant human TNF (rhTNF) were analyzed. Natural killer (NK) cell activity, TNF production, interleukin-1 (IL-1) production and mitogen-induced proliferation were measured either in whole blood samples or in cultures of peripheral mononuclear leukocytes of the patients directly before and after rhTNF infusion. NK cell activity, TNF and IL-1 production capacity and proliferative responses to concanavalin A (Con A) were significantly reduced after rhTNF application. We conclude from these observations that rhTNF in vivo acts directly or indirectly on NK cells and monocytes by either inactivating their functional capacity or by absorbing the relevant cells to the endothelial cell layer, thus removing them from circulation.


2019 ◽  
Vol 116 (35) ◽  
pp. 17409-17418 ◽  
Author(s):  
Xuefu Wang ◽  
Rui Sun ◽  
Xiaolei Hao ◽  
Zhe-Xiong Lian ◽  
Haiming Wei ◽  
...  

Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity by restraining NK cell maturation. It was observed that the development and metastasis of tumors were suppressed in IL-17A–deficient mice in the NK cell-dependent manner. In addition, the antiviral activity of NK cells was also improved in IL-17A–deficient mice. Mechanistically, ablation of IL-17A signaling promoted generation of terminally mature CD27−CD11b+ NK cells, whereas constitutive IL-17A signaling reduced terminally mature NK cells. Parabiosis or mixed bone marrow chimeras from Il17a−/−and wild-type (WT) mice could inhibit excessive generation of terminally mature NK cells induced by IL-17A deficiency. Furthermore, IL-17A desensitized NK cell responses to IL-15 and suppressed IL-15–induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) via up-regulation of SOCS3, leading to down-regulation of Blimp-1. Therefore, IL-17A acts as the checkpoint during NK cell terminal maturation, which highlights potential interventions to defend against tumors and viral infections.


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