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1.
Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.
Golebski, K, Layhadi, JA, Sahiner, U, Steveling-Klein, EH, Lenormand, MM, Li, RCY, Bal, SM, Heesters, BA, Vilà-Nadal, G, Hunewald, O, et al
Immunity. 2021;(2):291-307.e7
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Abstract
The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.
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High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study.
Miyoshi, Y, Yoshimura, Y, Saito, K, Muramoto, K, Sugawara, M, Alexis, K, Nomoto, K, Nakamura, S, Saeki, T, Watanabe, J, et al
Breast cancer (Tokyo, Japan). 2020;(4):706-715
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Abstract
BACKGROUND Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS). METHODS The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively. RESULTS Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin. DISCUSSION This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures. TRIAL REGISTRATION www.ClinicalTrials.gov code: NCT00388726.
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Acute glutamine ingestion modulates lymphocytic responses to exhaustive exercise in the heat.
Zheng, C, Chen, XK, Zhou, Y
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(3):213-220
Abstract
The purpose of this study was to determine if acute intake of glutamine modulates homeostatic, hematologic, immune, and inflammatory responses to exhaustive exercise in the heat. Thirteen healthy, untrained young men participated in this randomized, double-blind, placebo-controlled, crossover study. They served as their own control and completed 2 trials of treadmill exercise at 40% maximal oxygen uptake to exhaustion in a hot environment (temperature, 38.0 ± 1.0 °C; relative humidity, 60.0% ± 5.0%; oxygen, 20.8%) following placebo (PLA) and glutamine (GLN) consumption. Heart rate, gastrointestinal temperature, forehead temperature, the rating of perceived exertion, and body weight were measured. Blood samples were collected before and after exercise. After exhaustive exercise in the heat (PLA vs. GLN: 42.0 ± 9.5 vs. 39.6 ± 7.8 min, p > 0.05), significant changes in homeostatic, hematologic, and immune parameters (elevated natural killer (NK) cells and neutrophils, and reduced CD4+/CD8+ ratio and CD19+ lymphocytes) were found in the control group owing to the time effect (p < 0.05). Moreover, a condition × time interaction effect was observed for the absolute count of CD3+ (F = 4.26, p < 0.05) and CD3+CD8+ T lymphocytes (F = 4.27, p < 0.05), which were elevated following acute glutamine intervention. While a potential interaction effect was also observed for the absolute count of CD3+CD4+ T lymphocytes (F = 3.21, p = 0.08), no condition or interaction effects were found for any other outcome measures. The results of this study suggest that acute glutamine ingestion evokes CD3+ and CD3+CD8+ T lymphocytosis but does not modulate neutrophil and NK cell leukocytosis and immune disturbances after exhaustive exercise in the heat.
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Neutrophil:lymphocyte ratio is positively related to type 2 diabetes in a large-scale adult population: a Tianjin Chronic Low-Grade Systemic Inflammation and Health cohort study.
Guo, X, Zhang, S, Zhang, Q, Liu, L, Wu, H, Du, H, Shi, H, Wang, C, Xia, Y, Liu, X, et al
European journal of endocrinology. 2015;(2):217-25
Abstract
AIM: It is widely known that inflammation is related to type 2 diabetes (T2D), but few studies have shown a direct relationship between the immune system and T2D using a reliable biomarker. Neutrophil:lymphocyte ratio (NLR) is an easy-to-analyze inflammation biomarker, but few studies have assessed the relationship between NLR and T2D. In order to evaluate how NLR is related to T2D, we designed a large-scale cross-sectional and prospective cohort study in an adult population. SUBJECTS AND METHODS Participants were recruited from the Tianjin Medical University General Hospital-Health Management Centre. Both a baseline cross-sectional (n=87,686) and a prospective (n=38,074) assessment were performed. Participants without a history of T2D were followed up for ∼ 6 years (with a median follow-up of 2.7 years). Adjusted logistic and Cox proportional hazards regression models were used to assess relationships between the quintiles of NLR and T2D (covariates: age, sex, BMI, smoking status, drinking status, hypertension, hyperlipidemia, and family history of cardiovascular disease, hypertension, hyperlipidemia, or diabetes). RESULTS The prevalence and incidence of T2D were 4.9% and 6.8/1000 person-years respectively. The adjusted odds ratio and hazard ratio (95% CI) of the highest NLR quintile were 1.34 (1.21, 1.49) and 1.39 (1.09, 1.78) (both P for trend <0.01) respectively as compared to the lowest quintile of NLR. Leukocyte, neutrophil, and lymphocyte counts do not significantly predict the eventual development of T2D. CONCLUSION The present study demonstrates that NLR is related to the prevalence and incidence of T2D, and it suggests that NLR may be an efficient and accurate prognostic biomarker for T2D.
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Enteral nutrition supplemented with L-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection.
Cavalcante, AA, Campelo, MW, de Vasconcelos, MP, Ferreira, CM, Guimarães, SB, Garcia, JH, de Vasconcelos, PR
Nutrition (Burbank, Los Angeles County, Calif.). 2012;(4):397-402
Abstract
OBJECTIVE To evaluate the effect of enteral nutrition (EN) supplemented with l-glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. METHODS Thirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. RESULTS There were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0-47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. CONCLUSIONS The EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters.
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A combination of iron and retinol supplementation benefits iron status, IL-2 level and lymphocyte proliferation in anemic pregnant women.
Sun, YY, Ma, AG, Yang, F, Zhang, FZ, Luo, YB, Jiang, DC, Han, XX, Liang, H
Asia Pacific journal of clinical nutrition. 2010;(4):513-9
Abstract
BACKGROUND Iron and vitamin A deficiencies impact anemia and the immune system. OBJECTIVE to investigate the effect of iron combined with retinol supplementation on iron status, IL-2 level and lymphocyte proliferation. METHODS a double-blind randomized trial conducted over 2 months. We randomly allocated 186 anemic pregnant women with 80 ≤ Hb 0 < 110 g/L into four groups. Group I (n=47) was supplemented daily with 60 mg iron as ferrous sulfate, IF (n=46) with 60 mg iron and 0.4 mg folic acid, IR (n=46) with 60 mg iron, 2.0 mg retinol and 0.4 mg folic acid and C (n=47) was the placebo group,. RESULTS after the 2 months trial, there were considerable increases of iron status in Hb, plasma iron and ferritin in the I, IF and IR groups compared with Group C. Increases in plasma iron and ferritin in the IR group were also significantly greater than in Groups I and IF. Compared with group C, increases of IL-2 levels were 119, 184 and 206 ng/L; and lymphocyte proliferation increased by 0.095, 0.112 and 0.219 in Groups I, IF and IR, respectively. Increases of IL-2 were 65.3 ng/L and 87.5 ng/L in Groups IF and IR, greater than in Group I (both p values <0.01); and lymphocyte proliferation in Group IR were 0.124 and 0.107, also greater than in Groups I and IF, respectively. CONCLUSION iron combined retinol supplementation was more beneficial to improving iron status and lymphocyte proliferation during pregnancy than iron alone.
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Daily supplementation of tocotrienol-rich fraction or alpha-tocopherol did not induce immunomodulatory changes in healthy human volunteers.
Radhakrishnan, AK, Lee, AL, Wong, PF, Kaur, J, Aung, H, Nesaretnam, K
The British journal of nutrition. 2009;(6):810-5
Abstract
Vitamin E is divided into two subgroups; tocopherols and tocotrienols. Both have protective roles in biological systems. The present study was conducted to compare the effect of short-term supplementation at 200 mg/d of either alpha-tocopherol or a tocotrienol-rich fraction (TRF) from palm oil on immune modulation and plasma vitamin E levels in normal healthy Asian volunteers. In a randomised, double-blind placebo-controlled trial conducted, fifty-three healthy volunteers aged 20-50 years were recruited based on the study's inclusion and exclusion criteria. They were randomly assigned into three groups, i.e. two experimental groups that received daily supplementation at 200 mg of either alpha-tocopherol or the TRF, and the control group that received a placebo. Blood was drawn on days 0, 28 and 56 for several laboratory analyses. Differences in the production of IL-4 or interferon-gamma by concanavalin A-stimulated lymphocytes isolated from these volunteers were not significant (P>0.05). There were no significant differences observed in immune parameters between the healthy volunteers who received daily supplementation with either alpha-tocopherol or the TRF. As these observations were made in the absence of any immunogenic challenge, we feel it would be of benefit to study if there would be any differences observed when an immunogenic challenge such as vaccination were introduced.
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Influence of a high carbohydrate diet on the functional activity of 5-HT1B/1D receptors on human peripheral blood lymphocytes during intense military training.
Chennaoui, M, Drogou, C, Guezennec, CY, Gomez-Merino, D
European cytokine network. 2006;(1):67-74
Abstract
The present study was undertaken to examine the effect of a high carbohydrate diet on the functional activity of 5-HT1B/1D receptors in human peripheral blood lymphocytes, and on serum cortisol and plasma cytokine responses during intense military training. Thirty two male soldiers (mean age: 21 +/- 2 years) were randomly assigned to two groups and received either 3200 kcal/24 h [13440 kJ; habitual diet group (HD)] or 4200 kcal/24 h [17640 kJ, high carbohydrate diet group (HCD)] by adding 1000 kcal (4200 kJ) of fruit jelly to the HD. They took part in a three-week training program followed by a five-day combat course. Blood samples were collected from each group before entry into the commando training and after the five-day combat course. The results of [35S] GTPgammaS binding assays showed that h5-HT1B/1D receptors were desensitized after the training program in the HD group, whereas no change was observed between the beginning and the end of the military training in the HCD group [(HD : IC50 = 100 +/- 14 nM to 544 +/- 178 nM; n = 16) and (HCD: IC50 = 68 +/- 14 nM to 101 +/- 22 nM; n = 16)]. Serum cortisol was only significantly increased after the commando training in the HD group (from 532.2 +/- 30 to 642 +/- 45 nmol.L(-1), p < 0.05), whereas values were not significantly changed in the HCD group (441 +/- 31 to 502 +/- 40 nmol.L(-1)). No changes were observed in IL-10, TNF-alpha and IFN-gamma levels after the training program in either group. Carbohydrate ingestion or additional dietary energy during repeated bouts of high-intensity exercise could attenuate the alterations in immune function via 5-HT1B/1D receptors and the action of 5-HT moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) that specifically modulates the sensitivity of 5-HT1B/1D receptors.