Browsing by Subject "Cytokines"

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  • PRACTICAL Consortium; Bouras, Emmanouil; Karhunen, Ville; Gill, Dipender; Ahola-Olli, Ari; Mannikko, Minna; Auvinen, Juha; Herzig, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka; Lehtimäki, Terho; Salomaa, Veikko; Raitakari, Olli; Salmi, Marko; Jalkanen, Sirpa; Jarvelin, Marjo-Riitta; Tsilidis, Konstantinos K. (2022)
    Background Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. Methods Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). Results There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Conclusions Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.
  • Leppänen, Jonna; Randell, Kaisa; Schwab, Ursula; Pihlajamäki, Jussi; Romppanen, Jarkko; Keski-Nisula, Leea; Heinonen, Seppo; Laitinen, Tomi (2021)
    We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.
  • Peuhkuri, Katri; Vapaatalo, Heikki; Korpela, Riitta (2011)
  • Oksanen, Aino Mirjam; Haimila, Katri Eerika; Rautelin, Hilpi Iris Kaarina; Partanen, Jukka Antero (2010)
  • Kaartinen, Miia; Karlsson, Linnea; Paavonen, E. Juulia; Polo-Kantola, Päivi; Pelto, Juho; Nousiainen, Niko; Scheinin, Noora M.; Maksimow, Mikael; Salmi, Marko; Karlsson, Hasse (2019)
    Objective: Sleep disturbances relate to altered levels of inflammatory mediators in general population, but not much is known about the associations between sleep disturbances and inflammatory mediators during pregnancy. The present exploratory study investigated whether insomnia, tiredness, general sleep quality, and insufficient sleep duration during pregnancy relate to the concentrations of maternal peripheral circulating cytokines. As sleep disturbances are frequently observed in mood disorders, the results were controlled for symptoms of depression and anxiety. Methods: 137 participants were randomly drawn from a representative FinnBrain Birth Cohort. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from blood samples drawn at the gestational week 24. The sleep disturbances were evaluated using the Basic Nordic Sleep Questionnaire. Depressive and anxiety symptoms were measured with the Edinburgh Postnatal Depression Scale and the anxiety subscale of the self-rated Symptom Checklist 90, respectively. Results: Enhanced tiredness was associated with cytokine concentrations of IL-2, IL-10, IL-12, IL-13, and TNF-alpha. The observed associations resembled a reversed U-shaped curve rather than being linear. Having a good general sleep quality was associated with higher logarithmic cytokine concentrations of IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, and IFN-gamma. There was no evidence for associations between insomnia or sleep loss and cytokines. Conclusions: Maternal subjective tiredness and good general sleep quality were associated with altered levels of immunological markers during pregnancy. The association was independent from symptoms of depression and anxiety.
  • Wang, Qin; Wurtz, Peter; Auro, Kirsi; Makinen, Ville-Petteri; Kangas, Antti J.; Soininen, Pasi; Tiainen, Mika; Tynkkynen, Tuulia; Jokelainen, Jari; Santalahti, Kristiina; Salmi, Marko; Blankenberg, Stefan; Zeller, Tanja; Viikari, Jorma; Kahonen, Mika; Lehtimaki, Terho; Salomaa, Veikko; Perola, Markus; Jalkanen, Sirpa; Jarvelin, Marjo-Riitta; Raitakari, Olli T.; Kettunen, Johannes; Lawlor, Debbie A.; Ala-Korpela, Mika (2016)
    Background: Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood. Methods: Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status. Results: Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters. Conclusions: Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.
  • Dukay, Brigitta; Walter, Fruzsina R; Vigh, Judit P; Barabási, Beáta; Hajdu, Petra; Balassa, Tamás; Migh, Ede; Kincses, András; Hoyk, Zsófia; Szögi, Titanilla; Borbély, Emőke; Csoboz, Bálint; Horváth, Péter; Fülöp, Lívia; Penke, Botond; Vígh, László; Deli, Mária A; Sántha, Miklós; Tóth, Melinda E (BioMed Central, 2021)
    Abstract Background Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury. Methods In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry. Results Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions. Conclusions Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response.
  • Tolonen, Matti; Kuuliala, Krista; Kuuliala, Antti; Leppäniemi, Ari; Kylänpää, Marja-Leena; Sallinen, Ville; Puolakkainen, Pauli; Mentula, Panu (2019)
    Background: There is a wide variety of disease severity in patients with complicated intraabdominal infection (cIAI). The prognostic role of intraabdominal view (IAV) was recently studied, and an IAV score was introduced. The aim of this study was to analyze the associations between the preoperative levels of eight relevant circulating cytokines and IAV components, the IAV score, as well as outcome. Materials and methods: This was a single-center prospective study. The study cohort consisted of operatively managed adult patients with a cIAI. Preoperative plasma levels of eight cytokines were determined. The operating surgeon filled a form describing IAV. Outcomes analyzed were 30-day mortality and the development of organ dysfunctions requiring intensive care unit admission. Results: A total of 131 patients with cIAI were analyzed, 30-day mortality was 9.9% (n = 13), and 28 (21.4%) patients had postoperative organ dysfunctions. All components of IAV, the IAV score, and outcomes were associated with various cytokine levels. Interleukin-8 was the most competent marker associating with all the variables assessed in this study: diffuse peritonitis (P <0.001), substantial diffuse redness (P = 0.012), substantial diffuse fibrin (P = 0.003), fecal or bile as exudate (P = 0.001), nonappendiceal source of infection (P <0.001), IAV Score groups (P <0.001), organ dysfunctions (P <0.001), and 30-day mortality (P = 0.035). Conclusions: Various cytokines associate with the IAV and outcome. IL-8 showed the best overall performance. The results emphasize the role of the surgeons' perception of the IAV. IAV provides an approximation of the magnitude of the systemic inflammatory response. (C) 2019 Elsevier Inc. All rights reserved.
  • Simpson, Samantha; Kaislasuo, Janina; Guller, Seth; Pal, Lubna (2020)
    Background: The role of cytokines in various disease states is a burgeoning field of academic study and clinical application, however there are no consensus documents on how certain cytokines should be stored prior to quantification. This information is especially of interest to researchers assembling a biobank or clinicians who have to transport specimens to a different location in order to be tested. Objective: To review the literature and synthesize prior findings on cytokine storage and freeze/thaw stability. Design: We searched PubMed for articles related to cytokine storage stability. All articles were analyzed for cytokines studied, source of reported cytokine concentration (i.e., human whole blood or serum, concentrations from other species or bodily sources were excluded), and reported statistical results. Results: We identified and synthesized results of 23 peer-reviewed articles which published data on the storage and freeze/thaw stability of 33 different cytokines and chemokines. Conclusion: There is a wide variety of reported cytokine storage and freeze/thaw stability. Interleukin-6 and tumor necrosis factor alpha are the most widely studied cytokines in regard to temperature stability. In a few cytokines, a clear consensus can be reached as to storage safety at particular temperatures, but in most, more research needs to be done and we advise the clinician or researcher to use caution in interpreting cytokine concentration results after a long period of storage or several freeze/thaw cycles.
  • Nadella, Rasajna; Voutilainen, Merja H.; Saarma, Mart; Gonzalez-Barrios, Juan A.; Leon-Chavez, Bertha A.; Dueas Jimnez, Judith M.; Dueas Jimnez, Sergio H.; Escobedo, Lourdes; Martinez-Fong, Daniel (2014)
    BACKGROUND: The anti-inflammatory effect of the cerebral dopamine neurotrophic factor (CDNF) was shown recently in primary glial cell cultures, yet such effect remains unknown both in vivo and in 6-hydroxydopamine (6-OHDA) models of Parkinson's disease (PD). We addressed this issue by performing an intranigral transfection of the human CDNF (hCDNF) gene in the critical period of inflammation after a single intrastriatal 6-OHDA injection in the rat. METHODS: At day 15 after lesion, the plasmids p3xNBRE-hCDNF or p3xNBRE-EGFP, coding for enhanced green florescent protein (EGFP), were transfected into the rat substantia nigra (SN) using neurotensin (NTS)-polyplex. At day 15 post-transfection, we measured nitrite and lipoperoxide levels in the SN. We used ELISA to quantify the levels of TNF-α, IL-1β, IL-6, endogenous rat CDNF (rCDNF) and hCDNF. We also used qRT-PCR to measure rCDNF and hCDNF transcripts, and immunofluorescence assays to evaluate iNOS, CDNF and glial cells (microglia, astrocytes and Neuron/Glial type 2 (NG2) cells). Intact SNs were additional controls. RESULTS: In the SN, 6-OHDA triggered nitrosative stress, increased inflammatory cytokines levels, and activated the multipotent progenitor NG2 cells, which convert into astrocytes to produce rCDNF. In comparison with the hemiparkinsonian rats that were transfected with the EGFP gene or without transfection, 6-OHDA treatment and p3xNBRE-hCDNF transfection increased the conversion of NG2 cells into astrocytes resulting in 4-fold increase in the rCDNF protein levels. The overexpressed CDNF reduced nitrosative stress, glial markers and IL-6 levels in the SN, but not TNF-α and IL-1β levels. CONCLUSION: Our results show the anti-inflammatory effect of CDNF in a 6-OHDA rat of Parkinson's disease. Our results also suggest the possible participation of TNF-α, IL-1β and IL-6 in rCDNF production by astrocytes, supporting their anti-inflammatory role.