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1.
Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.
Fernandes, AL, Murai, IH, Reis, BZ, Sales, LP, Santos, MD, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, et al
The American journal of clinical nutrition. 2022;(3):790-798
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Abstract
BACKGROUND The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.
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Role of chemerin in the control of glucose homeostasis.
Léniz, A, González, M, Besné, I, Carr-Ugarte, H, Gómez-García, I, Portillo, MP
Molecular and cellular endocrinology. 2022;:111504
Abstract
Chemerin is an adipokine produced by the white adipose tissue and other tissues, which plays various roles in the pathogenesis of inflammatory and metabolic diseases in multiple organs. The present review aims at gathering scientific evidence reported in the last ten years, concerning the relationship of chemerin with alterations of glycaemic control, such as insulin resistance, type 2 diabetes and gestational diabetes in humans. Although the vast majority of the studies have shown a positive correlation between the chemerin level and a bad glycaemic control, a general consensus has not been reached. The reported results come from case-control and observational longitudinal studies, thereby limiting their interpretation. In fact, it cannot be stated whether insulin resistance and diabetes lead to an increase in chemerin levels or, on the contrary, if high levels of chemerin contribute to an impaired glycaemic control. Elevated levels of circulating chemerin are also associated with gestational diabetes mellitus. Chemerin gene polymorphisms could be proposed as mediators of glucose-related diseases. Nevertheless, to date very little is known about their implication in glucose metabolism. With regard to the mechanisms of action, chemerin impairs insulin cascade signaling by acting on several proteins of this cascade and by inducing inflammation.
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Chemokine-like MDL proteins modulate flowering time and innate immunity in plants.
Gruner, K, Leissing, F, Sinitski, D, Thieron, H, Axstmann, C, Baumgarten, K, Reinstädler, A, Winkler, P, Altmann, M, Flatley, A, et al
The Journal of biological chemistry. 2021;:100611
Abstract
Human macrophage migration inhibitory factor (MIF) is an atypical chemokine implicated in intercellular signaling and innate immunity. MIF orthologs (MIF/D-DT-like proteins, MDLs) are present throughout the plant kingdom, but remain experimentally unexplored in these organisms. Here, we provide an in planta characterization and functional analysis of the three-member gene/protein MDL family in Arabidopsis thaliana. Subcellular localization experiments indicated a nucleo-cytoplasmic distribution of MDL1 and MDL2, while MDL3 is localized to peroxisomes. Protein-protein interaction assays revealed the in vivo formation of MDL1, MDL2, and MDL3 homo-oligomers, as well as the formation of MDL1-MDL2 hetero-oligomers. Functionally, Arabidopsismdl mutants exhibited a delayed transition from vegetative to reproductive growth (flowering) under long-day conditions, but not in a short-day environment. In addition, mdl mutants were more resistant to colonization by the bacterial pathogen Pseudomonas syringae pv. maculicola. The latter phenotype was compromised by the additional mutation of SALICYLIC ACID INDUCTION DEFICIENT 2 (SID2), a gene implicated in the defense-induced biosynthesis of the key signaling molecule salicylic acid. However, the enhanced antibacterial immunity was not associated with any constitutive or pathogen-induced alterations in the levels of characteristic phytohormones or defense-associated metabolites. Interestingly, bacterial infection triggered relocalization and accumulation of MDL1 and MDL2 at the peripheral lobes of leaf epidermal cells. Collectively, our data indicate redundant functionality and a complex interplay between the three chemokine-like Arabidopsis MDL proteins in the regulation of both developmental and immune-related processes. These insights expand the comparative cross-kingdom analysis of MIF/MDL signaling in human and plant systems.
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Changes of omentin-1 and chemerin during 4 weeks of lifestyle intervention and 1 year follow-up in children with obesity.
Siegrist, M, Heitkamp, M, Braun, I, Vogg, N, Haller, B, Langhof, H, Koenig, W, Halle, M
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5648-5654
Abstract
AIMS: Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce. METHODS In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs). RESULTS Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p < 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p < 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p < 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p < 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p < 0.001). CONCLUSION Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss. TRIAL REGISTRATION ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.
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The kidney, COVID-19, and the chemokine network: an intriguing trio.
Taverna, G, Di Francesco, S, Borroni, EM, Yiu, D, Toniato, E, Milanesi, S, Chiriva-Internati, M, Bresalier, RS, Zanoni, M, Vota, P, et al
International urology and nephrology. 2021;(1):97-104
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Abstract
On December 30th 2019, some patients with pneumonia of unknown etiology were reported in the Program for Monitoring Emerging Diseases (ProMED), a program run by the International Society for Infectious Diseases (ISID), hypothesized to be related to subjects who had had contact with the seafood market in Wuhan, China. Chinese authorities instituted an emergency agency aimed at identifying the source of infection and potential biological pathogens. It was subsequently named by the World Committee on Virus Classification as 2019-nCoV (2019-novel coronavirus) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of studies have demonstrated that 2019-nCoV and the SARS-CoV shared the same cell entry receptor named angiotensin-converting enzyme 2 (ACE2). This is expressed in human tissues, not only in the respiratory epithelia, but also in the small intestines, heart, liver, and kidneys. Here, we examine the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, mainly acute kidney injury, and the potential role of the chemokine network.
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Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention.
Marti, A, Martínez, I, Ojeda-Rodríguez, A, Azcona-Sanjulian, MC
Nutrients. 2021;(2)
Abstract
Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (-43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.
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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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Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.
Muzzio, ML, Kabakian, ML, Morosán-Allo, Y, Ferrari, S, Fallahi, P, Fernández, J, Santucci, MP, Andrés-Lacueva, C, Antonelli, A, Brenta, G, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2020;(7):1188-1195
Abstract
BACKGROUND AND AIMS Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.
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Effect of Bariatric Surgery on the Circulating Level of Adiponectin, Chemerin, Plasminogen Activator Inhibitor-1, Leptin, Resistin, and Visfatin: A Systematic Review and Meta-Analysis.
Askarpour, M, Alizadeh, S, Hadi, A, Symonds, ME, Miraghajani, M, Sheikhi, A, Ghaedi, E
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(4):207-215
Abstract
Different adipokines secreted from adipose tissue, exert a range of physiological effects. The aim of present systematic review and meta-analysis was to critically investigate the consequence of bariatric surgery on circulating adipokines, that is, adiponectin, leptin, visfatin, resistin, plasminogen activator inhibitor, and chemerin. After systematically checking the following electronic databases: ISI web of Science, Scopus and PubMed without limitation in time and language up to February 2019, a pool based on a random effect model was established. Eighty-five eligible studies were entered for quantitative analysis. Our meta-analysis revealed that circulating adiponectin increased significantly after bariatric surgery [Standardized mean difference (SMD)=1.401, 95% CI: 1.101, 1.701, p<0.001]; whilst leptin (SMD=-2.178, 95% CI: -2.433, -1.923, p<0.001), PAI-1 (-14.928 ng/ml 95% CI: -21.794, -8.063, p<0.001), and chemerin (-50.238 ng/ml 95% CI: -85.708, -14.768, p<0.001) decreased. However, serum visfatin (2.05 ng/ml, 95% CI: -5.07, 9.17, p=0.573) and resistin (-2.080 ng/ml, 95% CI: -5.352, 1.192, p=0.21) were unchanged. In conclusion, bariatric surgery is associated with a reduction in specific adipokines including leptin, chemerin, and PAI-1, whereas adiponectin is raised, adaptations that could be indicative of improved fat mass and function.
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Cytokine and Chemokine Profile in Patients with Multiple Myeloma Treated with Bortezomib.
Robak, P, Węgłowska, E, Dróżdż, I, Mikulski, D, Jarych, D, Ferlińska, M, Wawrzyniak, E, Misiewicz, M, Smolewski, P, Fendler, W, et al
Mediators of inflammation. 2020;:1835836
Abstract
The aim of the study was to determine the levels of selected cytokines and chemokines in the serum of multiple myeloma (MM) patients treated with bortezomib-based regimens. A total of 71 MM patients were examined: 41 with primary refractory disease (17) or early relapse (28), and 30 who were bortezomib sensitive with no progression for at least six months. Patients who demonstrated CR or PR after bortezomib-based therapies longer than six months after treatment discontinuation were designated bortezomib sensitive. Serum cytokine levels were assayed with Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad). Higher levels of MIP-1α and lower levels of MIP-1β and IL-9 were associated with better responses to bortezomib-based treatment, and higher levels of IL-1ra and IL-8 were associated with bone involvement. MCP-1 was elevated in patients with hemoglobin < 10 g/dl compared to those without anemia. The levels of IL-8, MIP-1α, and TNF-α were significantly higher in patients with renal insufficiency. Only MIP-1α was elevated in patients with hypercalcemia compared to patients with normal calcium levels. In conclusion, distinct cytokines are involved in the pathogenesis of MM and may play a prominent role in the prediction of treatment response. However, a single measurement of serum cytokines should be interpreted with caution and further studies are needed.