Lacticaseibacillus rhamnosus modulates the inflammatory response and the subsequent lung damage in a murine model of acute lung inflammation

ABSTRACT Objective: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. Methods: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1β, IL-6, CXCL-1, TNF-α, TGF-β, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. Results: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. Conclusions: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.

Systemic inflammation and oxidative stress in adults with bronchiectasis: association with clinical and functional features

OBJECTIVES: To compare the inflammatory and oxidative stress (OS) states of adults with bronchiectasis with those of healthy controls and correlate inflammatory and OS levels with lung function and physical capacity. METHODS: This study used a cross-sectional design. Seventy-four adults with bronchiectasis (age: 49±15 years, forced expiratory volume in 1 second [FEV1]: 52.5±25.6%) and 42 healthy controls (age: 44±17 years, FEV1: 95.9±14.0%) performed cardiopulmonary exercise tests and incremental shuttle walking tests. Their physical activity in daily life, inflammatory cytokine, and antioxidant levels in plasma were measured. RESULTS: Compared to that of the controls, the levels of interleukin (IL)-6 (p<0.001), IL-10 (p<0.001), carbonylated proteins (p=0.001), and superoxide anions (p=0.046) were significantly increased in adults with bronchiectasis. Catalase activity was also reduced in this group (p<0.001). The inflammatory markers IL-1β, IL-6, and tumor necrosis factor-α correlated negatively with aerobic capacity (r=-0.408, r=-0.308, and r=-0.207, respectively). We observed similar correlations with OS markers (thiobarbituric acid and carbonyls; r=-0.290 and r=0.379, respectively), and these markers also significantly correlated with the aerobic capacity. CONCLUSIONS: Adults with bronchiectasis presented an increased systemic inflammatory response that correlated negatively with physical capacity.

The relationship of IL-8 and IL-10 myokines and performance in male marathon runners presenting exercise-induced bronchoconstriction

ABSTRACT: At present, it is unclear which exercise-induced factors, such as myokines, could diminish the negative impact of the reduction in pulmonary function imposed by the exercise in question. In this study, we aim to evaluate the prevalence of exercise-induced bronchoconstriction (EIB) and also to investigate the effect of myokines in the performance of marathon runners presenting EIB or not. Thirty-eight male recreational marathon runners (age 38.8 [33­44], height 175.7 [172.0­180.3]; weight 74.7 [69.3­81.6]) participated in this study, and through spirometry tests, a prevalence of 23.6% of EIB was found, which is in agreement with the literature. The volunteers who tested positive to EIB (EIB+) presented lower maximum aerobic capacity compared to those who tested negative (EIB−) (EIB+ 44.02 [39.56­47.02] and EIB− 47.62 [44.11­51.18] p = 0.03). The comparison of plasma levels of IL-1ß (EIB+ p = 0.296, EIB− p = 0.176, EIB+ vs. EIB− baseline p = 0.190 immediately after p = 0.106), IL-4 (undetectable), IL-6 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.301 immediately after p = 0.614), IL-8 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.110 immediately after p = 0.453), IL-10 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.424 immediately after p = 0.876) and TNF-α (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.141 immediately after p = 0.898) were similar in both groups 24 h before and immediately after the marathon. However, negative correlations were found between the marathon finishing time and the levels of IL-8 (r = −0.81, p = 0.022), and IL-10 (r = −0.97, p ≤ 0.001) immediately after completing the marathon. In conclusion, for the first time, it is shown that the myokines IL-8 and IL-10 are related to improvement of the performance of marathon runners presenting EIB.

Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis

Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group, 69 1±8 1 yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group, 72 0±6 4 yrs), not submitted to exercise training for at least 5 yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25 1±3 2 vs. 28 7±5 1, p < 0 05). The TRAINED group had lower glycemia (92 ± 3 vs. 118 ± 12, p < 0 05), glycated hemoglobin (5 9±0 1 vs. 6 4±0 2, p < 0 05), and triglycerides (98 (75-122) vs. 139 (109-214), p < 0 01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63), p < 0 01) and LDL-C/oxLDL ratio (13378 ± 2570 vs. 11639 ± 3113, p < 0 05) compared to the SED group. Proinflammatory cytokines as IL-1ß (11 31 ± 2 4 vs. 28 01 ± 4 7, p < 0 05), IL-6 (26 25 ± 7 4 vs. 49 41 ± 17 8, p < 0 05), and TNF-α (25 72 ± 2 8 vs. 51 73 ± 4 2, p < 0 05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26 3±7 4 vs. 49 0 ± 17 8, p < 0 05) and oxidized LDL (1551 ± 50 33 vs. 1773 ± 74, p < 0 02) and higher total antioxidant capacity (26 25 ± 7 4 vs. 49 41 ± 17 8, p < 0 001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.