Journal of Immunotoxicology最新文献

{"title":"Effect of lead exposure and nutritional iron-deficiency on immune response: A vaccine challenge study in rats.","authors":"Srinivasa Reddy Yathapu,&nbsp;Narendra Babu Kondapalli,&nbsp;Sarath Babu Srivalliputturu,&nbsp;Rajkumar Hemalatha,&nbsp;Dinesh Kumar Bharatraj","doi":"10.1080/1547691X.2020.1773973","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1773973","url":null,"abstract":"<p><p>The prevalence of iron (Fe) deficiency and subclinical lead (Pb) toxicity is high in developing countries like India, and information on their potential additive effects on immune responses is scant. The current study assessed immune parameters in dual Pb-exposedFe-deficient weanling SD rats. Rats were fed a control (CD) or Fe-deficient (ID) diet for 4 weeks and then evaluated for hemoglobin (Hb) and serum Fe status. Then, half the rats in each group began to receive daily oral Pb exposure (25 mg/4 ml/kg BW; gavage) or vehicle for a further 4 weeks (while maintained on original respective diets). After the 4-weeks of dosing, rats were assessed for Hb and serum Fe, and for blood lead level (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity. At this point, half the rats in each group (now <i>n</i> = 8) were then vaccinated with tetanus toxoid (TT), and then two boosters at 2-week intervals. All the time, rats stayed on their original respective diets along with exposure to Pb on alternate days. At 2 weeks after the final booster, rats were euthanized and blood collected to assess total/specific IgG and IgM levels; mucosal (intestinal) IgA levels were also determined. Spleens were taken to assess CD4⁺ and CD8⁺ cell levels and for <i>ex vivo</i> measures of splenocyte proliferation/T_H1 and T_H2 cytokine formation. The results indicated significant lowering of Hb and serum Fe levels in ID rats and increased blood Pb and decreased ALAD activity in all Pb-exposed rats. Fe-deficiency alone induced significant increases in ALAD activity, but only in an absence of Pb. While there was no impact of any regimen on total or TT-specific IgG, significant decreases in mucosal IgA and TT-specific IgM were seen in ID-fed Pb-exposed rats. CD4⁺ cell levels were not impacted by treatment; CD8⁺ levels were increased in all ID/Pb-exposed rats. <i>Ex-vivo</i> splenocyte proliferation was significantly higher among vaccinated rats, as well as ID-fed Pb-exposed unvaccinated rats. Cytokine formation in all cases was highly variable. The results suggest that Fe deficiency compromised cell-mediated, mucosal, and/or humoral immune response-related endpoints and that Pb exposure during the deficiency further impacted these outcomes.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"144-152"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1773973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38080081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental pollutants modulate RNA and DNA virus-activated miRNA-155 expression and innate immune system responses: Insights into new immunomodulative mechanisms.","authors":"Alexander Badry,&nbsp;Veerle L B Jaspers,&nbsp;Courtney A Waugh","doi":"10.1080/1547691X.2020.1740838","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1740838","url":null,"abstract":"<p><p>Many persistent organic pollutants, such as polychlorinated biphenyls (PCBs), have high immunomodulating potentials. Exposure to them, in combination with virus infections, has been shown to aggravate outcomes of the infection, leading to increased viral titers and host mortality. Expression of immune-related microRNA (miR) signaling pathways (by host and/or virus) have been shown to be important in determining these outcomes; there is some evidence to suggest pollutants can cause dysregulation of miRNAs. It was thus hypothesized here that modulation of miRNAs (and associated cytokine genes) by pollutants exerts negative effects during viral infections. To test this, an <i>in vitro</i> study on chicken embryo fibroblasts (CEF) exposed to a PCB mixture (Aroclor 1260) and then stimulated with a synthetic RNA virus (poly(I:C)) or infected with a lymphoma-causing DNA virus (Gallid Herpes Virus 2 [GaHV-2]) was conducted. Using quantitative real-time PCR, expression patterns for <i>mir-155</i>, pro-inflammatory <i>TNF</i>α and <i>IL-8</i>, transcription factor <i>NF-</i>κ<i>B1</i>, and anti-inflammatory <i>IL-4</i> were investigated 8, 12, and 18 h after virus activation. The study showed that Aroclor1260 modulated <i>mir-155</i> expression, such that a down-regulation of <i>mir-155</i> in poly(I:C)-treated CEF was seen up to 12 h. Aroclor1260 exposure also increased the mRNA expression of pro-inflammatory genes after 8 h in poly(I:C)-treated cells, but levels in GaHV-2-infected cells were unaffected. In contrast to with Aroclor1260/poly(I:C), Aroclor1260/GaHV-2-infected cells displayed an increase in <i>mir-155</i> levels after 12 h compared to levels seen with either individual treatment. While after 12 h expression of most evaluated genes was down-regulated (independent of treatment regimen), by 18 h, up-regulation was evident again. In conclusion, this study added evidence that <i>mir-155</i> signaling represents a sensitive pathway to chemically-induced immunomodulation and indicated that PCBs can modulate highly-regulated innate immune system signaling pathways important in determining host immune response outcomes during viral infections.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"86-93"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1740838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37790588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium induces CCL2 production in glioblastoma cells via activation of MAPK, PI3K, and PKC pathways.","authors":"Thitima Kasemsuk,&nbsp;Suttinee Phuagkhaopong,&nbsp;Ruedeemars Yubolphan,&nbsp;Norapat Rungreangplangkool,&nbsp;Pornpun Vivithanaporn","doi":"10.1080/1547691X.2020.1829211","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1829211","url":null,"abstract":"<p><p>Cadmium (Cd) is accumulated in human astrocytes and induces the production of interleukin (IL)-6 and IL-8. Astrocytes are one of the major sources of chemokine C-C motif ligand 2 (CCL2; known as monocyte chemoattractant protein-1 [MCP-1]), in the brain. Elevated CCL2 levels are associated with cognitive impairment as well as the migration and invasion of glioblastoma cells. The present study hypothesized that non-toxic concentrations of Cd (as cadmium chloride [CdCl₂]) could up-regulate CCL2 production in U-87 MG human glio-blastoma cells. The results showed that after exposure of the U-87 MG cells to CdCl₂ at 1 and 10 µM, there was an up-regulation of <i>CCL2</i> mRNA expression after 3 h of exposure and increased CCL2 secretion after 6 and 24 h. The study also found that inhibition of MAPK pathways, including ERK1/2, p38, and JNK by U0126, SB203580 and SP600125, respectively, reduced Cd-induced CCL2 secretion by the cells. Moreover, when cells were pretreated with Ro 32-0432 (an inhibitor of calcium-dependent PKC) and LY294002 (a PI3K inhibitor), this also resulted in a down-regulation of any Cd-induced CCL2 expression. Taken together, the results of this study allow for the conclusion to be made that CCL2 up-regulation in U-87 MG cells induced by Cd is mediated, in part, by an activation of MAPK, PI3K/Akt, and PKC pathways.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"186-193"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1829211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38505155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model.","authors":"Lisa M Plitnick,&nbsp;Beth Hutchins,&nbsp;Sheri Dubey,&nbsp;Nianyu Li,&nbsp;Rupesh P Amin,&nbsp;Stephanie Born,&nbsp;Ruban Mangadu,&nbsp;Joseph H Phillips,&nbsp;Venkataraman Sriram,&nbsp;Danuta J Herzyk","doi":"10.1080/1547691X.2020.1826020","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1826020","url":null,"abstract":"<p><p>The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint which may be engaged by cells in a tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda^®) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG₄/κ isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. The current work was focused on developing a mouse T-Dependent Antibody Response (TDAR) model using a murinized rat anti-mouse PD-1 antibody (muDX400; a rodent surrogate for pembrolizumab) to evaluate the potential impact of treatment with a PD-1 inhibitor on immune responses to an antigen challenge (e.g. HBsAg in Hepatitis B vaccine). Despite the lower binding affinity and T_1/2 compared to pembrolizumab, ligand blocking data indicated muDX400 had appropriate pharmacological activity and demonstrated efficacy in mouse tumor models, thus was suitable for pharmacodynamic and vaccination studies in mice. In a vaccination study in which mice were concomitantly administered muDX400 and the Hepatitis B vaccine, muDX400 was well-tolerated and did not result in any immune-mediated adverse effects. The treatment with muDX400 was associated with a shift in the ratio between naive and memory cells in both CD4⁺ and CD8⁺ T-lymphocytes in the spleen but did not affect anti-HBsAg antibody response profile. The mouse TDAR model using the Hepatitis B vaccine and the surrogate anti-PD1 monoclonal antibody was a useful tool in the evaluation of the potential immune-mediated effects of pembrolizumab following vaccination and appears to be a suitable alternative for the nonhuman primate TDAR models utilized for other checkpoint inhibitors.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"175-185"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1826020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38603560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating inflammatory markers in cervical cancer patients and healthy controls.","authors":"Agne Vitkauskaite,&nbsp;Daiva Urboniene,&nbsp;Joana Celiesiute,&nbsp;Kristina Jariene,&nbsp;Erika Skrodeniene,&nbsp;Ruta Jolanta Nadisauskiene,&nbsp;Daiva Vaitkiene","doi":"10.1080/1547691X.2020.1755397","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1755397","url":null,"abstract":"<p><p>There is increasing evidence that host inflammatory responses play an important role in the development and progression of cancers. There are some data that cancer is associated not only with inflammation at the site of the lesion, but also with dysregulations of the host overall systemic immune response. In the case of cervical cancer, inflammation is an important factor associated with the development, progression, and potential metastasis of the disease. What is unclear still in the potential for modifications of host responses to human papillomaviruses (HPV) - a known causative agent of CC, that could be induced by cigarette smoking. In particular, it remains to be determined how the inflammation induced by HPV infection could impact on CC incidence/severity. In this prospective study, serum levels of 10 cytokines were evaluated using Multiplex and ELISA assays. The samples were the sera of 43 CC patients and 60 healthy (NILM) controls. All outcomes were evaluated in relation to host HPV and to their smoking status. The results in indicated that serum sTREM-1, TNFα, IFNβ, IL-1β, and IL-6 levels were significantly increased in CC (HPV+) patients compared to healthy NILM controls. A similar trend was observed for IL-10 and IL-2 levels. Within the two groups, differences in cytokine levels between smokers and never smokers were not remarkable. The findings here support the hypothesized role of systemic inflammation in the pathophysiology of CC.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"105-109"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1755397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37898532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics.","authors":"Cris Kamperschroer,&nbsp;Jacintha Shenton,&nbsp;Hervé Lebrec,&nbsp;John K Leighton,&nbsp;Paul A Moore,&nbsp;Oliver Thomas","doi":"10.1080/1547691X.2020.1729902","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1729902","url":null,"abstract":"<p><p>Currently, there is a multitude of CD3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. The key safety concerns with CD3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (CRS), target organ toxicity due to redirection of T-cells to normal tissues expressing the tumor-associated antigen (TAA) (off-tumor/on-target cytotoxicity), and, in some instances, neurotoxicity. Another key challenge is to arrive at a safe clinical starting dose and an efficient escalating strategy that allows patients in early dose cohorts the potential for clinical benefit in Phase 1 trials. To expand the therapeutic index and bring more treatment options to patients, there are intense efforts to overcome these challenges through improvements in molecular design, preclinical safety assessment strategies, and clinical management practices. A recent workshop at the U.S. Food and Drug Administration (FDA) with industry, academic, and regulatory agency representation was held to discuss the challenges and explore where such improvements to the development of CD3 bispecifics can be implemented. Here, the content of the presentations and the discussion that occurred during this workshop are summarized.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"67-85"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1729902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37678768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.","authors":"Hong-Soo Lee,&nbsp;Doo-Wan Cho,&nbsp;Ji-Seok Han,&nbsp;Su-Cheol Han,&nbsp;Sang Keun Woo,&nbsp;Soo-Youn Jun,&nbsp;Woo-Jong Lee,&nbsp;Susie Yoon,&nbsp;Son-Il Pak,&nbsp;Sang-Jin Lee,&nbsp;Eunsol Seong,&nbsp;Eun-Jung Park","doi":"10.1080/1547691X.2019.1699617","DOIUrl":"https://doi.org/10.1080/1547691X.2019.1699617","url":null,"abstract":"<p><p>In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co⁶⁰ γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 μg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"31-42"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2019.1699617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37607108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunostimulatory effects on THP-1 cells by peptide or protein pharmaceuticals associated with injection site reactions.","authors":"Eri Hamamura-Yasuno,&nbsp;Tetsuo Aida,&nbsp;Yoshimi Tsuchiya,&nbsp;Kazuhiko Mori","doi":"10.1080/1547691X.2020.1727071","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1727071","url":null,"abstract":"<p><p>Injection site reaction (ISR) is a common side-effect associated with the use of peptide or protein pharmaceuticals. These types of pharmaceuticals-induced activation of antigen-presenting cells is assumed to be a key step in the pathogenesis of immune-mediated ISR. The present study was designed to evaluate the immunostimulatory properties of peptide or protein pharmaceuticals using human monocytic THP-1 cells. Here, THP-1 cells, with or without phorbol-12-myristate-13-acetate (PMA) pretreatment, were exposed to enfuvirtide and glatiramer acetate (positive controls) or evolocumab (negative control) for 6 or 24 h. PMA treatment differentiated non-adherent monocytic THP-1 (nTHP-1) cells into adherent macrophagic THP-1 (pTHP-1) cells that highly express CD11b and CD36. Enfuvirtide increased the release of cytokines, e.g. TNFα, MIP-1β, and MCP-1, and expression of CD86 and CD54 on nTHP-1 cells at 24 h. Similar immunostimulatory properties of glatiramer acetate were observed both in the nTHP-1 and pTHP-1 cells at 6 h, but the responses were very weak in the pTHP-1 cells. Evolocumab did not affect cytokine secretion or cell surface marker expression in either cell type. Taken together, these <i>in vitro</i> THP-1 cell assays revealed the immunostimulatory properties of enfuvirtide and glatiramer acetate. This assay platform thus could serve as a powerful tool in evaluating potential immune-related ISR risks of peptide or protein pharmaceuticals in humans.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"59-66"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1727071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37670523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-company evaluation of the human lymphocyte activation assay.","authors":"Mark Collinge,&nbsp;Patricia Schneider,&nbsp;Dingzhou Li,&nbsp;Stanley Parish,&nbsp;Carolyne Dumont,&nbsp;Wendy Freebern,&nbsp;Joseph Ghanime,&nbsp;Fanny Guimont-Derochers,&nbsp;Anja Langenkamp,&nbsp;Jose Lebron,&nbsp;Nianyu Li,&nbsp;Celine Marban,&nbsp;Lisa Plitnick,&nbsp;Jennifer Wheeler","doi":"10.1080/1547691X.2020.1725694","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1725694","url":null,"abstract":"<p><p>Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One <i>in vitro</i> assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the <i>in vivo</i> T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies. The HuLA assay requires less time and drug than TDAR assays, uses a relevant antigen (influenza), reflects a human immune response, and applies principles of the 3Rs to non-clinical safety assessment. Peripheral blood mononuclear cells (PBMC) from flu-immunized donors are re-stimulated with flu-vaccine in the presence of test articles, and proliferation is measured. Published data demonstrate the applicability of the HuLA assay, but it has not been evaluated for reproducibility across testing sites. To evaluate assay reproducibility, scientists from a consortium of institutions conducted the assay in parallel, using a common pool of donor PBMC, influenza vaccine, and known immunosuppressant compounds (cyclosporine A and mycophenolic acid). The HuLA assay was highly reproducible in identification of inhibition of antigen-specific responses, and there was significant agreement across testing sites in the half maximal inhibitory concentration (IC₅₀) values. Intra-site variability was the largest contributor to the variability observed within the assay. The HuLA assay was demonstrated to be ideally suited to comparing multiple compounds (i.e. compound ranking or benchmarking) within the same assay. Overall, the data reported herein support the HuLA assay as a useful tool in mechanistic evaluations of antigen-specific immune responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"51-58"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1725694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37699770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local inflammatory marker production in Lithuanian patients with chronic rhinosinusitis with nasal polyps.","authors":"Justinas Vaitkus,&nbsp;Astra Vitkauskiene,&nbsp;Vilte Matuseviciute,&nbsp;Albinas Naudziunas,&nbsp;Nora Siupsinskiene,&nbsp;Saulius Vaitkus","doi":"10.1080/1547691X.2020.1850938","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1850938","url":null,"abstract":"<p><p>There are two clinical subtypes of chronic rhinosinusitis (CRS): chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The aim of the study here was to determine the levels of invasive inflammatory markers in nasal mucosa samples taken from CRSwNP patients during the surgery and to identify markers that could serve as targets for potential clinical and therapeutic interventions. The study was carried out in 59 patients with proven CRSwNP and a control group consisting of 52 healthy individuals. Concentrations of the inflammatory markers of interest were determined using a LuminexR Assay multiplex kit. The data obtained indicated that levels of inflammatory cytokines interleukin (IL)-2, -4, -5, -7, -12, -17 and -22 were all significantly higher in the nasal polyps (NP) than those in the mucosa of control participants. No differences were seen between the study groups for IL -6, -10, -13, -21 and interferon (IFN)-γ. OR (Odds Ratio) analyses confirmed that elevations in mucosal levels of IL-2, -4, -5, -7, -12, -17, and -22 were likely immune markers of CRSwNP. In conclusion, the present study demonstrated that IL-2, -4, -12 and -22 may be important in the etiopathogenesis of CRSwNP; as markers, each show moderate sensitivity, but high specificity in the Lithuanian population. IL-17 had good sensitivity, but low specificity in the CRSwNP patients.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"202-206"},"PeriodicalIF":3.3,"publicationDate":"2020-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1850938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38363160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}