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Does intestinal dysbiosis contribute to an aberrant inflammatory response to severe acute respiratory syndrome coronavirus 2 in frail patients?
Terruzzi, I, Senesi, P
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110996
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Abstract
In a few months, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main health problem worldwide. Epidemiologic studies revealed that populations have different vulnerabilities to SARS-CoV-2. Severe outcomes of the coronavirus disease 2019 (COVID-19) with an increased risk of death are observed in patients with metabolic syndrome, as well as diabetic and heart conditions (frail population). Excessive proinflammatory cytokine storm could be the main cause of increased vulnerability in this frail population. In patients with diabetes and/or heart disease, a low inflammatory state is often associated with gut dysbiosis. The increase amount of microbial metabolites (i.e., trimethylamine N-oxide and lipopolysaccharide), which generate an inflammatory microenvironment, is probably associated with an improved risk of severe illness from COVID-19. Nutritional interventions aimed at restoring the gut microbial balance could represent preventive strategies to protect the frail population from COVID-19. This narrative review presents the possible molecular mechanisms by which intestinal dysbiosis that enhances the inflammatory state could promote the spread of SARS-CoV-2 infection. Some nutritional strategies to counteract inflammation in frail patients are also analyzed.
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Effects of canola or olive oil on plasma lipids, lipoprotein-associated phospholipase A2 and inflammatory cytokines in patients referred for coronary angiography.
Khandouzi, N, Zahedmehr, A, Nasrollahzadeh, J
Lipids in health and disease. 2020;(1):183
Abstract
BACKGROUND The potential cardioprotective benefits of olive oil (OO) and canola oil (CO) consumption have been shown in some studies. The present study compared the effects of CO and OO on plasma lipids, some inflammatory cytokines, and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity in patients undergoing coronary angiography. METHODS The current randomized, controlled, parallel-arm, clinical trial involved 48 patients (44 men and 4 women, aged 57.63 ± 6.34 years) with at least one classic cardiovascular risk factor (hypertension, dyslipidemia, or diabetes) who referred for coronary angiography. Patients were randomly divided into two groups and received 25 mL/day refined olive oil (n = 24) or canola oil (n = 24) for 6 weeks. Plasma lipids, some selected inflammatory markers, and Lp-PLA2 levels were measured at baseline and after the intervention. RESULTS CO consumption produced a significant reduction in plasma Lp-PLA2 mass (- 0.97 ± 1.84 vs. 0.34 ± 1.57 ng/mL, p = 0.008 for CO and OO, respectively), whereas the mean changes in interleukine-6 concentration were significantly lower after OO consumption compared with CO (- 9.46 ± 9.46 vs. -0.90 ± 6.80 pg/mL, p = 0.008 for OO and CO, respectively). After 6 weeks of intervention, no significant changes were observed in plasma Lp-PLA2 activity, complement C3, C4, or lipid profiles in the two intervention groups. CONCLUSIONS Comparing the two vegetable oils in subjects with cardiovascular risk factors showed that the consumption of olive oil is more effective in reducing the level of inflammatory cytokine interleukine-6, whereas canola oil was more effective in lowering Lp-PLA2 levels; however, this finding should be interpreted with caution, because Lp-PLA2 activity did not change significantly. TRIAL REGISTRATION IRCT20160702028742N5 at www.irct.ir (04/19/2019).
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Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy.
Antonelli, A, Fallahi, P, Elia, G, Ragusa, F, Paparo, SR, Ruffilli, I, Patrizio, A, Gonnella, D, Giusti, C, Virili, C, et al
Best practice & research. Clinical endocrinology & metabolism. 2020;(1):101388
Abstract
Graves' disease (GD) is characterized by thyrotoxicosis, caused by the presence of circulating thyroid stimulating antibodies (TSAb), that are determinant also in the pathogenesis of its extrathyroidal manifestations [Graves' ophthalmopathy (GO), pretibial myxedema]. T helper (Th)1 immune response prevails in the immune-pathogenesis of GD and GO, during the active phase, when Th1 chemokines, and their (C-X-C)R3 receptor, play a key role. In GD, the existing treatments are not ideal for hyperthyroidism (long-term remission with anti-thyroid-drugs only in 50% of patients; while radioiodine and surgery cause hypothyroidism). In GD, antigen-specific therapy has been recently published, with the induction of T cell tolerance via an immunization by TSH-R peptides. In GO, rituximab and drugs targeting cytokines have been evaluated. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody) showed to be very effective in GO patients. Further researches are necessary to identify novel effective therapies targeting GD, or GO.
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Effects of short-term xylitol chewing gum on pro-inflammatory cytokines and Streptococcus mutans: A randomised, placebo-controlled trial.
Akgül, Ö, Topaloğlu Ak, A, Zorlu, S, Öner Özdaş, D, Uslu, M, Çayirgan, D
International journal of clinical practice. 2020;(9):e13623
Abstract
INTRODUCTION Dental caries is an infectious disease with predominantly of cariogenic bacteria such as Streptococcus mutans (S mutans). Xylitol is considered as one of the effective agents that can limit this dental infection. In this randomised, placebo-controlled trial, we aimed to evaluate the potential reflection of short-term xylitol consumption on pro-inflammatory cytokines (TNF-α, IL-6 and IL-8) and S mutans counts by ELISA and qPCR (Quantitative real-time PCR), respectively. METHODS In this study, 154 participants were assigned to two groups, control and xylitol. Dental examination, saliva and swab samples were done at baseline and at 3-week for clinical and microbiological assessment. RESULTS In xylitol group at the end of 3-week, gingival and plaque index scores were significantly decreased with respect to baseline values (P < .001 and P < .05, respectively). The salivary concentration of TNF-α, IL-6 and IL-8 were statistically declined at 3-week, more so than those at baseline in xylitol group (P < .001). S mutans expression was reduced about fivefold at 3-week use of xylitol and it was a statistically significant difference compared to baseline (P < .001). CONCLUSION Intriguingly, even short-term consumption of xylitol might play a favourable role in maintaining the oral health status, possibly as a result of decreasing the release of pro-inflammatory cytokines and the counts of S mutans. Nonetheless, this investigation warrants further endorsement.
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An inflammatory stimulus sensitizes TRPA1 channel to increase cytokine release in human lung fibroblasts.
Yap, JMG, Ueda, T, Takeda, N, Fukumitsu, K, Fukuda, S, Uemura, T, Tajiri, T, Ohkubo, H, Maeno, K, Ito, Y, et al
Cytokine. 2020;:155027
Abstract
External stimuli such as cigarette smoke and house dust mite are often involved in the development and exacerbation of asthma. These risk factors could activate or sensitize transient receptor potential channel ankyrin 1 (TRPA1), which are primarily expressed in neuronal structures but also in non-neuronal cells such as fibroblasts. However, the role of non-neuronal TRPA1 in the pathophysiology of airway diseases including asthma remains unclear. We investigated TRPA1 expression on human fibroblast cells and whether inflammatory mediators could modulate its function. This study utilized human lung fibroblast cell lines, Medical Research Council cell strain 5 (MRC-5) and HF19 cells frequently used on experimental studies regarding allergic and respiratory disorders. The human lung fibroblasts were stimulated with house dust mite (Der p1) or tumor necrosis factor alpha (TNF-α) for 24 h, and we quantified TRPA1 mRNA and protein by qRT-PCR and western blot analysis, respectively. TRPA1 mRNA expressions were upregulated after TNF-α treatment. Calcium imaging analysis revealed that TNF-α treatment apparently sensitized TRPA1-mediated calcium influx by TRPA1 agonist allyl isothiocyanate (AITC) and the selective TRPA1 channel blocker HC-030031 effectively reduced the calcium response. Lastly, TRPA1 activation was not only involved in increased IL-8 cytokine release, but also in upregulating gene expression of matrix metalloprotease 9 (MMP9) in the human lung fibroblasts treated with TNF-α Together, these results indicate that presence of inflammatory mediators such as TNF-α could upregulate the non-neuronal expression of TRPA1 on fibroblasts which may aggravate further the release of inflammatory cytokines observed in human airway diseases.
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Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.
Fiorino, S, Gallo, C, Zippi, M, Sabbatani, S, Manfredi, R, Moretti, R, Fogacci, E, Maggioli, C, Travasoni Loffredo, F, Giampieri, E, et al
Aging clinical and experimental research. 2020;(10):2115-2131
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Abstract
BACKGROUND In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.
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Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.
Villa, G, Romagnoli, S, De Rosa, S, Greco, M, Resta, M, Pomarè Montin, D, Prato, F, Patera, F, Ferrari, F, Rotondo, G, et al
Critical care (London, England). 2020;(1):605
Abstract
BACKGROUND Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.
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Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome.
Fuentes, GC, Castañer, O, Warnberg, J, Subirana, I, Buil-Cosiales, P, Salas-Salvadó, J, Corella, D, Serra-Majem, L, Romaguera, D, Estruch, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3092-3098
Abstract
BACKGROUND There is limited prospective evidence on the association between physical activity (PA) and inflammation in older adults. Our aim was to assess the associations between changes in PA and changes in the inflammatory profile in older individuals who are overweight or obese. METHODS This prospective study included 489 men and women, aged 55-75 years, from the PREDIMED-Plus trial. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), monocyte chemo-attractant protein-1 (MCP-1), C-peptide, high-sensitivity C-reactive protein (hs-CRP), leptin, and regulated on activation, normal T-cell expressed and secreted chemokine (RANTES) were obtained from fasting blood samples and a composite inflammatory score based on these biomarkers was calculated. Physical activity was measured by a validated questionnaire. All measures were taken at baseline and one-year follow-up. RESULTS Multiple linear regression models showed an association between an increase in total PA and a decrease in the inflammatory score (p = 0.012), which was particularly driven by a decrease in C-peptide (p = 0.037). Similarly, the inflammatory score decreased with increasing moderate PA (p = 0.001), and moderate-to-vigorous PA (p = 0.006). CONCLUSIONS Increases in total PA, moderate and moderate-to-vigorous PA were associated with a decrease in the inflammatory profile of obese or overweight older individuals. This finding is relevant for PA recommendations and public health strategies. CLINICAL TRIAL REGISTRY Clinical trial identifier: International Standard Randomized Controlled Trial 89898870.
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Altered monocyte phenotype and dysregulated innate cytokine responses among people living with HIV and opioid-use disorder.
Underwood, ML, Nguyen, T, Uebelhoer, LS, Kunkel, LE, Korthuis, PT, Lancioni, CL
AIDS (London, England). 2020;(2):177-188
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Abstract
BACKGROUND Opioid-use disorders (OUD) and hepatitis C or B co-infection (HEP) are common among people living with HIV (PLHIV). The impact of OUD on innate and adaptive immunity among PLHIV with and without HEP is unknown. OBJECTIVES To investigate the impact of OUD on monocyte and T-cell phenotypes, cytokine responses to lipopolysaccharide (LPS) and phytohemagglutinin (PHA), and plasma inflammatory markers, among PLHIV with and without HEP. METHODS Cross-sectional study enrolling PLHIV receiving ART, with and without OUD. Flow cytometry determined monocyte and T-cell phenotypes; LPS and PHA-induced cytokine production was assessed following LPS and PHA stimulation by multiplex cytokine array; plasma IL-6, soluble CD163, and soluble CD14 were measured by ELISA. RESULTS Twenty-two PLHIV with OUD and 37 PLHIV without OUD were included. PLHIV with OUD exhibited higher frequencies of intermediate (CD14CD16) and nonclassical (CD14CD16) monocytes when compared with PLHIV without OUD (P = 0.0025; P = 0.0001, respectively), regardless of HEP co-infection. Soluble CD163 and monocyte cell surface CD163 expression was increased among PLHIV with OUD and HEP, specifically. Regardless of HEP co-infection, PLHIV with OUD exhibited reduced production of IL-10, IL-8, IL-6, IL-1alpha, and TNF-alpha in response to LPS when compared with PLHIV without OUD; PHA-induced production of IL-10, IL-1alpha, IL-1beta, IL-6, and TNF-alpha were also reduced among individuals with OUD. CONCLUSION OUD among PLHIV are associated with altered monocyte phenotypes and a dysregulated innate cytokine response. Defining underlying mechanisms of opioid-associated innate immune dysregulation among PLHIV should be prioritized to identify optimal OUD treatment strategies.
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Visfatin as a predictor of obstructive sleep apnea in atrial fibrillation patients.
Szymanska, A, Platek, AE, Sierdzinski, J, Szymanski, FM
Sleep & breathing = Schlaf & Atmung. 2020;(3):1215-1218
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Abstract
BACKGROUND Obstructive sleep apnea (OSA) often coexists with atrial fibrillation (AF) and makes the course of AF worse. The negative impact of OSA on AF may be due to atrial stretch, hypoxia, hypertension, obesity, fibrosis, and inflammation. Several mediators are thought to be responsible for this correlation, among them adipokines such as visfatin. This study aimed to assess the association between visfatin concentrations and OSA in patients with AF. AIMS This study aimed to assess the association between visfatin concentrations and OSA in AF patients. METHODS In a tertiary Cardiology Department, hospitalized patients previously diagnosed with AF were enrolled in the study. Diagnosis of OSA was made based on a respiratory polygraphy and patients had blood samples taken for assessment of plasma visfatin concentration. RESULTS A total of 266 patients with AF (65% men, age 57.6 ± 10.1) were enrolled, and 121 (45%) were diagnosed with OSA. Patients with OSA had higher visfatin concentrations than those without OSA (2.13 ± 0.17 vs. 1.70 ± 0.21 ng/mL; p = 0.04). Patients with mild OSA had visfatin levels equal to 1.77 ± 0.17 ng/mL, moderate OSA 2.38 ± 0.18 ng/mL, and severe OSA 3.55 ± 0.61 ng/mL (p for trend = 0.017). Multivariate regression analysis showed that increased visfatin concentrations were associated with the risk of OSA (odds ratio 1.92; 95% confidence interval 1.09-3.40). CONCLUSIONS Patients with AF who were diagnosed with OSA had significantly higher plasma visfatin levels which increased according to the severity of OSA. Furthermore, multivariate regression analysis identified visfatin concentration over 1.25 ng/mL, male sex, age over 59.1 years, and permanent AF as the factors showing independent correlation with OSA.