Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies

The effects of radiotherapy on systemic immunity remain to be fully characterized in a disease-specific manner. The aim of the study was to examine potential biomarkers of systemic immunomodulation when using radiotherapy for thoracic malignancies. Serial blood samples were collected from 56 patients with thoracic malignancies prior (RTbaseline), during (RTduring) and at the end of radiotherapy (RTend), as well as at the first (FU1) and second follow-up (FU2). The changes in serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF-α, bFGF, sFlt-1, PlGF, VEGF, VEGF-C, VEGF-D and HGF were measured by multiplexed array and tested for associations with clinical outcomes. We observed an increase in the levels of IL-10, IFN-γ, PlGF and VEGF-D and a decrease in those of IL-8, VEGF, VEGF-C and sFlt-1 during and at the end of radiotherapy. Furthermore, baseline concentration of TNF-α significantly correlated with OS. IL-6 level at RTend and FU1,2 correlated with OS (RTend: p = 0.039, HR: 1.041, 95% CI: 1.002–1.082, FU1: p = 0.001, HR: 1.139, 95% CI: 1.056–1.228, FU2: p = 0.017, HR: 1.101 95% CI: 1.018–1.192), while IL-8 level correlated with OS at RTduring and RTend (RTduring: p = 0.017, HR: 1.014, 95% CI: 1.002–1.026, RTend: p = 0.004, HR: 1.007, 95% CI: 1.061–1.686). In conclusion, serum levels of TNF-α, IL-6 and IL-8 are potential biomarkers of response to radiotherapy. Given the recent implementation of immunotherapy in lung and esophageal cancer, these putative blood biomarkers should be further validated and evaluated in the combination or sequential therapy setting.

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Serum Levels of Cytokines and Cytokine Receptors Are Associated with Outcome in Newly Diagnosed AML Patients

Blood ◽

10.1182/blood.v128.22.5246.5246 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5246-5246 ◽

Cited By ~ 1

Author(s):

Tomas Kupsa ◽

Jan Vanek ◽

Pavel Zak ◽

Ladislav Jebavy ◽

Jan M. Horacek

Keyword(s):

Growth Factor ◽

Risk Stratification ◽

Serum Levels ◽

Cytokine Receptors ◽

Newly Diagnosed ◽

Gm Csf ◽

Tnf Α ◽

Ifn Γ ◽

Metalloproteinase 9

Abstract Background: Cytokines, cytokine receptors and adhesion molecules have been studied as markers of immune system activation in various diseases including AML/MDS. These factors form a dynamic network which affects AML cell susceptibility to chemotherapy. To provide more evidence of these interactions, we analyzed the serum levels of a broad panel of cytokines, cytokine receptors, matrix metalloproteinase-9 and soluble adhesion molecules. Aims: The aim of our study was to evaluate hypothesis that baseline serum levels of these factors are associated with relapse and overall survival (OS). Methods: A total of 65 AML patients (27 males, 38 females, mean age 53.7 ± 12.8, median 57.1 years) newly diagnosed in the period 2011 - 2014 were analyzed. All patients were Caucasian. Of these, 14 had better risk, 10 intermediate-1 risk, 13 intermediate-2 risk and 28 high risk AML according to ELN risk stratification (Döhner et al., Blood 2010). The NPM-1 was mutated in 16 cases, the FLT3-ITD was present in 15 cases. The secondary disease was present in 26 cases, 3 patients were BCR/ABL positive. Five patients with APL were treated with the PETHEMA regimen combining Idarubicin and All-trans retinoic acid (ATRA). All other patients were induced with "3+7" induction chemotherapy consisting of Cytarabin 100mg/m2 per day for 7 consecutive days and Daunorubicin 90mg/m2 for the first 3 days of therapy in younger patients. In patients aged ≥ 65 years, Daunorubicin 45-60mg/m2 was administered, depending on patient WHO performance status. We evaluated baseline circulating levels of the following factors: interleukins (IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-15), epidermal growth factor (EGF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-gamma (IFN-γ), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), matrix-metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2), E-selectin (E-SEL), P-selectin (P-SEL), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Statistical analysis was performed in R 3.1.2. Probability values (P) < 0.05 were considered statistically significant. Results: All evaluated analytes were independent of age, disease origin and ELN risk stratification. Relapse occurred in 34 cases with median of 516 days. Median follow-up was 627 days. Primary AML, normal karyotype and achieving of complete remission (CR) after induction therapy were associated with better relapse free survival (RFS), whereas higher TNFR-1, VEGF, IL-3, TNFR-2, NPM-1 and BCR/ABL were associated with inferior RFS. OS correlated with levels of IFN-γ, GM-CSF and TNFR-1. In multivariate analysis, primary AML, higher IL-10 and IL-15 were associated longer OS. Higher age, higher ELN risk and higher levels of TNFR-1, IL-3, IL-6, IL-8 and TNFR-2 were associated with inferior OS. Conclusions: Cytokines are an important part of cancer environment. In AML, some cytokines or their receptors may be informative for individual prognosis. The literature suggests association of IL-6 and IL-10 levels and OS (Correa et al., Cytokine 2013). Our data are in agreement with this finding, but revealed more cytokines and their receptors, especially TNFR-1, which were independently associated with relapse and OS. To confirm these findings, analysis in a larger cohort with longer follow-up should be performed. Acknowledgment: The work was supported by a specific research project "Analysis of defined prognostic factors in acute myeloid leukemia" (FMHS Hradec Kralove), by a long-term organization development plan 1011 (FMHS Hradec Kralove) and by MH CZ - DRO (UHHK, 00179906). Disclosures No relevant conflicts of interest to declare.

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High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽

10.3390/life11060527 ◽

2021 ◽

Vol 11 (6) ◽

pp. 527

Author(s):

Lucero A. Ramon-Luing ◽

Ranferi Ocaña-Guzman ◽

Norma A. Téllez-Navarrete ◽

Mario Preciado-García ◽

Dámaris P. Romero-Rodríguez ◽

...

Keyword(s):

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Control Group ◽

Hiv Patients ◽

Art Initiation ◽

Tnf Α ◽

Ifn Γ ◽

Α Level ◽

Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

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Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-6392 ◽

2014 ◽

Vol 66 (4) ◽

pp. 1067-1072

Author(s):

M.A.R. Feliciano ◽

A.S.L. Silva ◽

R.M. Crivelaro ◽

M.E.F. Oliveira ◽

L.N. Coutinho ◽

...

Keyword(s):

Immune Response ◽

Natural Killer ◽

Serum Levels ◽

Blood Samples ◽

Tnf Α ◽

Ifn Γ ◽

Pathological Pregnancy ◽

English Bulldog

The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer) in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA) validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05). However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

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Novel Diagnostic Approaches to Adamantiades-Behcet's Disease

European Journal of Inflammation ◽

10.1177/1721727x0500300208 ◽

2005 ◽

Vol 3 (2) ◽

pp. 103-108

Author(s):

M. Hatzistilianou ◽

S. Hitoglou ◽

D. Gougoustamou ◽

M. Antoniades ◽

S. Pappa ◽

...

Keyword(s):

Serum Levels ◽

Posterior Uveitis ◽

Vegf Inhibitors ◽

Tnf Α ◽

Inactive Period ◽

Diagnostic Approaches ◽

Effect Of Treatment ◽

Genital Ulcers ◽

The Right

A 10 year old boy had visual deterioration in both eyes. Visual acuity was 0.2 in the right and 0.3 in the left eye. Further ophthalmologic findings were typical of posterior uveitis. The pediatric physical examination also disclosed aphthous stomatitis and recurrent aphthous genital ulcers. At diagnosis serum levels of IL-1β, IL-6, IL-8, TNF-α, sIL-2R, MCP-1, VEGF, tADA activity in the patient with active and ABD relapse were significantly higher than those in the inactive period of the disease, suggesting that these parameters may be related to disease activity. In addition to the proinflammatory chemokines and cytokines, plasma levels of VEGF and serum tADA activity may be used for the diagnosis of ABD and for monitoring the effect of treatment, as well as the follow-up period. Also, further studies of VEGF may lead to novel therapies with antibodies or other VEGF inhibitors.

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Inflammatory and immunogenetic markers in correlation with pulmonary tuberculosis

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132013000600011 ◽

2013 ◽

Vol 39 (6) ◽

pp. 719-727 ◽

Cited By ~ 3

Author(s):

Beatriz Lima Alezio Muller ◽

Daniela Maria de Paula Ramalho ◽

Paula Fernanda Gonçalves dos Santos ◽

Eliene Denites Duarte Mesquita ◽

Afranio Lineu Kritski ◽

...

Keyword(s):

Inflammatory Response ◽

Pulmonary Tuberculosis ◽

Gene Polymorphisms ◽

Serum Levels ◽

Acute Inflammatory Response ◽

Reactive Protein ◽

Antituberculosis Treatment ◽

Tnf Α ◽

Referral Hospitals ◽

Ifn Γ

OBJECTIVE: To describe serum levels of the cytokines IL-10, TNF-α, and IFN-γ, as well as polymorphisms in the genes involved in their transcription, and their association with markers of the acute inflammatory response in patients with pulmonary tuberculosis.METHODS: This was a descriptive, longitudinal study involving 81 patients with pulmonary tuberculosis treated at two referral hospitals. We collected data on sociodemographic variables and evaluated bacteriological conversion at the eighth week of antituberculosis treatment, gene polymorphisms related to the cytokines studied, and serum levels of those cytokines, as well as those of C-reactive protein (CRP). We also determined the ESR and CD4+ counts.RESULTS: The median age of the patients was 43 years; 67 patients (82.7%) were male; and 8 patients (9.9%) were infected with HIV. The ESR was highest in the patients with high IFN-γ levels and low IL-10 levels. IFN-γ and TNF-α gene polymorphisms at positions +874 and −238, respectively, showed no correlations with the corresponding cytokine serum levels. Low IL-10 levels were associated with IL-10 gene polymorphisms at positions −592 and −819 (but not −1082). There was a negative association between bacteriological conversion at the eighth week of treatment and CRP levels.CONCLUSIONS: Our results suggest that genetic markers and markers of acute inflammatory response are useful in predicting the response to antituberculosis treatment.

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Early Disease Relapse after Tyrosine Kinase Inhibitor Treatment Discontinuation in CML Is Related Both to Low Number and Impaired Function of NK-Cells

Blood ◽

10.1182/blood.v124.21.812.812 ◽

2014 ◽

Vol 124 (21) ◽

pp. 812-812 ◽

Cited By ~ 7

Author(s):

Mette Matilda Ilander ◽

Ulla Olsson-Strömberg ◽

Hanna Lähteenmäki ◽

Kasanen Tiina ◽

Perttu Koskenvesa ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Research Funding ◽

Nk Cell ◽

Treatment Discontinuation ◽

Disease Relapse ◽

Cell Counts ◽

Tnf Α ◽

Ifn Γ

Abstract Background: Recent reports suggest that approximately 40% of CML patients who have achieved sustained complete molecular remission are able to stop TKI treatment without disease relapse. However, there are no predictive markers for successful therapy discontinuation. Therefore, we set up an immunological sub-study in the ongoing pan-European EURO-SKI stopping study. Our aim was to identify predictive biomarkers for relapse/non-relapse and to understand more on the mechanisms of immune surveillance in CML. Methods: The EURO-SKI study started in 2012, and patients included were at least three years on TKI and at least one year in MR4 or deeper before the study entry. Basic lymphocyte immunophenotyping (the number of NK-, T- and B-cells) was performed at the time of therapy discontinuation and 1, 6, and 12 months after the TKI stop and in case of relapse (defined as loss of MMR, BCR-ABL1>0.1% IS). In addition, from a proportion of patients more detailed immunophenotypic and functional analyses (cytotoxicity of NK-cells and secretion of Th1 type of cytokines IFN-γ/TNF-α) were done at the same times. Results: Thus far 119 Nordic patients (imatinib n=105, dasatinib n=12, nilotinib n=2) who have discontinued TKI treatment within the EURO-SKI study have been included in the lymphocyte subclass analysis (results are presented from patients who have reached 6 months follow-up). Immunophenotyping analysis demonstrates that imatinib treated patients who were able to maintain remission for 6 months (n=36) had increased NK-cell counts (0.26 vs. 0.15x109cells/L, p=0.01, NK-cell proportion 18.9% vs. 11%, p=0.005) at the time of drug discontinuation compared to patients who relapsed early (before 5 months n=22). Furthermore, the phenotype of NK-cells was more cytotoxic (more CD57+ and CD16+cells and less CD62L+cells), and also their IFN-γ/TNF-α secretion was enhanced (19.2% vs. 13%, p=0.02). Surprisingly, patients who relapsed more slowly (after 5 months, n=16) had similar baseline NK-cell counts (0.37x109cells/L), NK-cell proportion (21.2%), and phenotype and function as patients, who were able to stay in remission. No differences in the NK-cell counts were observed between patients who had detectable or undetectable BCR-ABL1 transcripts at the baseline (0.22 x109cells/L vs. 0.31 x109cells/L, p=0.61). Interestingly, NK-cell count was higher in patients with low Sokal risk score than in patients with intermediate risk (0.33 x109cells/L vs. 0.20 x109cells/L, p=0.04). Furthermore, there was a trend that male patients had a higher proportion of NK-cells than females (21.6% vs. 15.7%, p=0.06). Pretreatment with IFN-α or the duration of imatinib treatment did not have an effect on NK-cell count or proportion. In comparison to the imatinib group, dasatinib treated patients had higher NK-cell counts at the baseline (median 0.52x109cells/L vs. 0.26x109cells/L, p=0.02), and also the proportion of CD27 (median 50% vs. 16%, p=0.01) and CD57 expressing (median 79% vs. 74%, p=0.05) NK-cells was higher. The follow-up time of dasatinib treated patients is not yet long enough to correlate the NK-cell counts with the success of the treatment discontinuation. The absolute number of T-cells or their function did not differ significantly between relapsing and non-relapsing patients at the time of treatment discontinuation. However, both CD4+ and CD8+ T-cells tended to be more mature in patients who stayed in remission compared to patients who relapsed early (CD4+CD57+CD62L- median 5.7% vs. 2.4%, p=0.06, CD8+CD62L+CD45RA+ 13% vs. 26.7%, p=0.05). The analysis of follow-up samples showed that in patients who stayed in remission the Th1 type cytokine (IFN-γ/TNF-α) secretion of CD8+T-cells increased at 6 months compared to baseline (23.6 vs. 18.5%, p=0.07). Same phenomenon was observed in the late relapsing group at relapse compared to baseline (37.9 vs. 13.5%, p=0.03). No similar increase was observed in the early relapsing group. Conclusions: Low NK-cell numbers and poor cytokine secretion may predict early disease relapse after TKI discontinuation. However, patients who relapse later have high numbers of normally functioning NK-cells. Further research (detailed phenotypic analysis of NK- and T-cells including activating and inhibitory receptors and immune checkpoint molecules) and correlation of biomarker data with clinical parameters are ongoing to understand the ultimate determining factors of relapse. Disclosures Själander: Novartis: Honoraria. Hjorth-Hansen:Novartis: Honoraria; Bristol-myers Squibb: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding. Mustjoki:Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

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Curcumin Ameliorate Diabetes type 1 Complications through Decreasing Pro-inflammatory Cytokines in C57BL/6 Mice

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v19i(s1.r1).2854 ◽

2020 ◽

Author(s):

Yaser Jafari Khataylou ◽

Somayeh Ahmadiafshar ◽

Reza Rezaei ◽

Saeid Parsamanesh ◽

Golbahar Hosseini

Keyword(s):

Serum Levels ◽

Treated Group ◽

Diabetic Group ◽

Enzyme Linked Immunosorbent Assay ◽

Diabetic Mice ◽

Citrate Buffer ◽

C Peptide ◽

Tnf Α ◽

Ifn Γ

Type 1 diabetes is a chronic autoimmune disease of beta cells in the islets of Langerhans, which are responsible for making insulin. Even with insulin therapy, inflammatory complications will develop in the long term. The present study examines changes in serum levels of interleukin (IL)-6, IL-17, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-peptide, Insulin as well as fasting blood sugar (FBS) in control, diabetic and diabetic treated with curcumin groups. Thirty inbred C57BL /6 mice were randomly divided into three groups of 10 mice: group A consisted of healthy mice receiving citrate buffer, group B included a group of diabetic mice, and group C was a group of diabetic mice treated with curcumin. The cytokine levels were measured in the supernatant of stimulated splenocytes using enzyme -linked immunosorbent assay (ELISA). Radioimmunoassay was used to measure insulin and c-peptide levels. The FBS was measured by an automatic glucometer device. The levels of IL-6, IL-17, and IFN-γ, as well as FBS, was significantly decreased in the treated group with curcumin compared to the diabetic group mice (p<0.05). TNF-α levels were also low, but the difference was not significant. IL-10, plasma C-peptide, and insulin significantly increased in the supernatant of stimulated splenocytes of treated diabetic group than in the diabetic group (p<0/05). According to the results, this study supports the anti-diabetic and anti-inflammatory effects of curcumin; however, more studies are needed to investigate theeffects of curcumin and the dose-response relationship in this disease.

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CCL2 is Modulated by Cytokines and PPAR-γ in Anaplastic Thyroid Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170719152349 ◽

2018 ◽

Vol 18 (3) ◽

pp. 458-466 ◽

Cited By ~ 5

Author(s):

Silvia Martina Ferrari ◽

Giusy Elia ◽

Simona Piaggi ◽

Enke Baldini ◽

Salvatore Ulisse ◽

...

Keyword(s):

Anaplastic Thyroid Cancer ◽

Serum Levels ◽

Anaplastic Thyroid Carcinoma ◽

Ppar Γ ◽

Tnf Α ◽

Proliferation And Apoptosis ◽

Different Types ◽

Level Versus ◽

Ifn Γ ◽

Growth Promoting

Background and Objective: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. Methods: We tested in “primary human anaplastic thyroid carcinoma (ATC) cells” (ANA) versus “normal thyroid follicular cells” (TFC): a) CCL2 secretion basally, after IFN-γ and/or TNF-α stimulation; b) PPARγ activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA. Results: ANA produced basally CCL2, at a higher level versus TFC. IFN-γ or TNF-α dose-dependently induced the CCL2 release in 3/6 or 5/6 ANA, respectively, but in all TFC. IFN-γ+TNF-α induced a synergistic release of CCL2 in all TFC, but only in 1/6 ATC. TZDs exerted an inhibition of CCL2 release in 3/6 ANA, while had no effect in TFC. Pioglitazone inhibition of ANA proliferation was not associated with the effect on CCL2; NF-κB and ERK1/2 were basally activated in ANA, increased by IFN-γ+TNF-α, and pioglitazone inhibited IFN- γ+TNF-α activation. CCL2 serum levels were higher in 6 ATC patients than in 5 controls (813±345 versus 345±212, pg/mL; respectively; P<0.01, ANOVA). Conclusion: ANA produce CCL2 basally and after cytokines stimulation, with an extremely variable pattern of modulation, suggesting different types of deregulation in the chemokine modulation. Serum CCL2 is increased in ATC patients. Further studies will be necessary to evaluate if CCL2 might be used as a marker in the followup of ATC patients.

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Early cytokine response after vaccination with Coxiella burnetii phase I in an infected herd of dairy cattle

Journal of Veterinary Research ◽

10.2478/jvetres-2018-0076 ◽

2018 ◽

Vol 62 (4) ◽

pp. 469-476

Author(s):

Joanna Małaczewska ◽

Edyta Kaczorek-Łukowska ◽

Monika Szymańska-Czerwińska ◽

Wojciech Rękawek ◽

Roman Wójcik ◽

...

Keyword(s):

T Lymphocyte ◽

Q Fever ◽

Serum Levels ◽

Aetiological Agent ◽

Infected Herd ◽

Animal Blood ◽

Post Vaccination ◽

Vaccination Response ◽

Tnf Α ◽

Ifn Γ

AbstractIntroduction:Coxiella (C.) burnetii, the aetiological agent of Q fever, is able to modulate the macrophage/T-lymphocyte axis in an infected organism and impair synthesis of monokines and lymphokines.Material and Methods: The purpose of this research was to determine the levels of the cytokines that play a key role in the response to C. burnetii antigens (IL-1β, IL-2, IL-6, IL-10, IFN-γ and TNF-α) in the serum of animals originating from an infected herd prior to vaccination (day 0) and at 1, 7, and 21 days afterwards.Results: The vaccination of animals did not affect the production of IL-6, IL-1β, or IL-2. The serum levels of these cytokines were too low to measure in most of the samples. The initial levels of TNFα, IFNγ, and IL-10 were higher in seropositive than in seronegative animals, although significant differences between seropositive shedders and seropositive nonshedders appeared only in the levels of IFNγ and IL-10. Additionally, the course of the post-vaccination response concerning these two cytokines was different among seronegative nonshedders, seropositive nonshedders, and seropositive shedders.Conclusion: It seems that analysis of the IFNγ and IL-10 concentrations in animal blood serum may have some practical value in an assessment of the health status of seropositive animals and post-vaccination response.

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Neopterin and Cytokines in Non-pleocytotic Cerebrospinal Fluid in Child Patients

Pteridines ◽

10.1515/pteridines.2000.11.4.142 ◽

2000 ◽

Vol 11 (4) ◽

pp. 142-146

Author(s):

Yasuhiko Kawakami ◽

Kentaro Kuwabara ◽

Takehisa Fujita ◽

Osamu Fujino ◽

Yoshitaka Fukunaga

Keyword(s):

Cerebrospinal Fluid ◽

Immune Activation ◽

Serum Levels ◽

Microglial Cells ◽

Febrile Convulsions ◽

Exanthem Subitum ◽

Tnf Α ◽

Child Patients ◽

Ifn Γ

Abstract CSF and serum levels of neopterin and several kinds of CSF cytokines were measured in child patients with non-pleocytotic CSF. The CSF neopterin levels with febrile convulsions (FCs) were 27.4±33.0 nmol/1 and the CSF neopterinlserum neopterin ratio (C/S ratio) with FCs was 2.07±2.06. The longer the FCs patients' convulsions lasted, the higher their CSF neopterin levels tended to be come. The CSF neopterin levels with FCs were significantly higher than in those with pyrexia without convulsions (6.5±2.5 nmol/L) or convulsions without pyrexia, including epilepsy (4.9±2.9 nmol/L). The C/S ratio was also higher in patients with FCs than in those with pyrexia without convulsions (0.31±0.17) or convulsions without pyrexia (0.82±0.50).In addition, there was a tendency for CSF IFN-γ levels to be higher in patients with FCs than in those with pyrexia without convulsions or convulsions without pyrexia. However, TNF-α and IL-1α were under measurable levels in cases of non-pi eocytotic CSF. The CSF neopterin levels in patients with exanthem subitum with FCs were higher than in those without FCs. It has been reported that there is a possibility of neopterin production by microglial cells. Our finding that CSF neopterin levels were elevated in patients with FCs, whose CSF had no pleocytosis, are consistent with the possibility of neopterin production by microglia. Our results further suggest that immune activation of microgrial cells is one of the mechanisms involved in the onset of FCs.

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