scholarly journals An observational study of innate immune responses in patients with acute appendicitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toon Peeters ◽  
Sandrina Martens ◽  
Valentino D’Onofrio ◽  
Mark H. T. Stappers ◽  
Jeroen C. H. van der Hilst ◽  
...  
Keyword(s):  
Acute Appendicitis ◽  
Immune Responses ◽  
Complicated Appendicitis ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
Serum Cytokine ◽  
Post Surgery ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Recognition Receptor

Abstract Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.

scholarly journals Reactive arthritis and undifferentiated peripheral spondyloarthritis share human leucocyte antigen B27 subtypes and serum and synovial fluid cytokine profiles

Rheumatology ◽  
2020 ◽  
Author(s):  
Jyoti Ranjan Parida ◽  
Sandeep Kumar ◽  
Sakir Ahmed ◽  
Smriti Chaurasia ◽  
Ratnadeep Mukherjee ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Human Leucocyte Antigen ◽  
Healthy Controls ◽  
Hla B27 ◽  
Serum Cytokine ◽  
Cytokine Profiles ◽  
Cytokine Levels ◽  
Peripheral Spondyloarthritis ◽  
Multiplex Cytokine ◽  
Age And Sex

Abstract Objectives Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA. Methods ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels. Results In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients. Conclusion ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.

Effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal cord of diabetic rats

2020 ◽  
Vol 16 (4) ◽  
pp. 293-301
Author(s):  
A. Kaki ◽  
M. Nikbakht ◽  
A.H. Habibi ◽  
H.F. Moghadam
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Immune Responses ◽  
Diabetic Neuropathy ◽  
Aerobic Exercise ◽  
Inflammatory Mediators ◽  
Innate Immune ◽  
Moderate Intensity ◽  
Innate Immune Responses ◽  
Tnf Α

Neuronal inflammation is one of the pathophysiological causes of diabetes neuropathic pain. The purpose of this research was to determine the effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal dorsal horn in rats with diabetic neuropathic pain. 40 eight-week-old male Wistar rats (weight range 220±10.2 g) were randomly divided into four groups of (1) sedentary diabetic neuropathy (SDN), (2) training diabetic neuropathy (TDN), (3) training control (TC), and (4) sedentary control (SC). Diabetes was induced by injection of streptozocin (50 mg/kg). Following confirmation of behavioural tests for diabetes neuropathy, the training groups performed 6 weeks of moderate-intensity aerobic exercise on the treadmill. The expression of Toll like receptor (TLR)4, TLR2, tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 genes in L4-L6 spinal cord sensory neurons was measured by Real Time PCR. Two-way ANOVA and Bonferroni’s post hoc tests were used for statistical analysis. After performing aerobic exercise protocol, the TDN compared to the SDN showed a significant decrease in the mean score of pain in the formalin test and a significant increase in the latency in Tail-Flick test was observed. The expression of TLR4, TLR2, TNF-α and IL-1β genes was significantly higher in the SDN than in the SC group (P<0.05). The expression of the above genes in the TDN was significantly lower than the SDN group (P<0.05). Also, the expression level of IL-10 gene was significantly higher in the TDN than the SDN group (P<0.05). Aerobic exercise improved sensitivity of nociceptors to pain-inducing agents in diabetic neuropathy due to inhibition of inflammatory receptors and increased levels of anti-inflammatory agents in the nervous system. Thus, aerobic exercise should be used as a non-pharmacological intervention for diabetic patients to reduce neuropathic pain.

scholarly journals The expression and significance of inflammatory cytokines and MMP-9 in the tears of the infected eye and contralateral uninfected eye in patients with fungal keratitis

2021 ◽  
Author(s):  
Shuang Zhang ◽  
Hui-Min Wu ◽  
Xiang-Ni Cao ◽  
Xian-Qi Zhang ◽  
Gui-ping Gao
Keyword(s):  
Tear Film ◽  
Fungal Keratitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Controls ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Healthy Control ◽  
The Relationship ◽  
Tear Film Function

Abstract Background: We investigated bilateral tear cytokine levels including interleukin (IL)-1β, IL-10, IL-17, tumor necrosis factor (TNF)-α and Matrix metalloproteinase-9 (MMP-9) in patients with fungal keratitis(FK). Meanwhile, we evaluated the relationship between the changes of tear cytokines with corneal perception and pain in infected eyes, and the relationship between tear cytokines and tear film function in contralateral uninfected eyes .Methods : A total of 60(20 FK, 20 contralateral, 20 healthy controls) tear samples were collected prospectively and analyzed by enzyme linked immunosorbent assay(ELISA). Approximately 50 to 60 ul of tear samples in each case were collected. Meanwhile ,we analyzed the changes of visual analogue scale(VAS), tear breakup time (TBUT), Schirmer I test (SIT) and corneal perception compared with healthy controls. Results :The concentrations of IL-1β, IL-10 and IL-17 increased in bilateral eyes compared with healthy controls(P<0.05). The tear concentrations of MMP-9 , TNF-α only significantly increased in affected eyes (P <0.05). Patients with FK showed significant reduction in corneal perception of infected eyes compared with controls(P<0.05). Corneal perception of the normal eyes in FK patients was slightly lower than that of control group, but there was not statistical difference (P>0.05).TBUT and SIT of contralateral uninfected eyes were significantly lower than that of control group(P<0.05), which were significantly correlated with levels of IL-1β, IL-17(P<0.05). SIT were also negatively correlated with MMP-9(P<0.05), while the levels of IL-1β, IL-10, IL-17, TNF-α and MMP-9 in the tears of the healthy control group had no significant correlation with TBUT and SIT indicators(P>0.05).The corneal perception and VAS score of the affected FK eyes showed correlation with IL-1β, IL-17 and TNF-α(P<0.05).In addition, concentration of IL-10 inversely was correlated with VAS (P<0.05). Conclusion: Proinflammatory tear cytokines are elevated in bilateral eyes with unilateral FK as associated with tear film function ,pain and corneal sensitivity.

Genetic association of IL-6, TNF-α and SDF-1 polymorphisms with serum cytokine levels in diabetic foot ulcer

Gene ◽  
2015 ◽  
Vol 565 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Umapathy Dhamodharan ◽  
Vijay Viswanathan ◽  
Ezhilarasi Krishnamoorthy ◽  
Rama Rajaram ◽  
Vivekanandhan Aravindhan
Keyword(s):  
Genetic Association ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Serum Cytokine ◽  
Tnf Α ◽  
Cytokine Levels

scholarly journals Fungal Exposure and Low Levels of IL-10 in Patients with Sarcoidosis

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Marjeta Terčelj ◽  
Sanja Stopinšek ◽  
Alojz Ihan ◽  
Barbara Salobir ◽  
Saša Simčič ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Healthy Controls ◽  
Serum Cytokine ◽  
Fungal Cell ◽  
Fungal Exposure ◽  
Cytokine Levels ◽  
Exposure Levels ◽  
Low Levels ◽  
Anti Inflammatory Cytokine

Background and Objectives. Sarcoidosis is an inflammatory disease with increased levels of inflammatory cytokines. Previous studies have shown a relation between the degree of granuloma infiltration and serum cytokine levels, except for interleukin- (IL-) 10. The aim of the study was to further investigate the serum levels of IL-10 in patients with sarcoidosis and relate them to fungal exposure in terms of the amount of fungi in the air of their homes andβ-glucan in bronchoalveolar lavage (BAL) fluid.Methods. Patients with sarcoidosis (n=71) and healthy controls (n=27) were enrolled. IL-10 was determined in serum. BAL was performed and the amount ofβ-glucan was measured. Domestic exposure to fungi was determined by measuring airborneβ-N-acetylhexosaminidase (NAHA) in the bedrooms.Results. At high levels of fungal exposure (domestic fungal exposure andβ-glucan in BAL), serum IL-10 values were lower than at low and intermediate exposure levels.Conclusion. The low serum IL-10 values at high fungal exposure suggest that fungal cell wall agents play a role in granuloma formation in sarcoidosis by inhibiting the secretion of the anti-inflammatory cytokine IL-10.

scholarly journals The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Díaz-Alvarez ◽  
Enrique Ortega
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Terminal Protein ◽  
Molecular Pattern ◽  
Evolutionarily Conserved ◽  
Carbohydrate Recognition Domains ◽  
Galectin 3 ◽  
The Many ◽  
Recognition Receptor

Galectins are a group of evolutionarily conserved proteins with the ability to bindβ-galactosides through characteristic carbohydrate-recognition domains (CRD). Galectin-3 is structurally unique among all galectins as it contains a C-terminal CRD linked to an N-terminal protein-binding domain, being the only chimeric galectin. Galectin-3 participates in many functions, both intra- and extracellularly. Among them, a prominent role for Galectin-3 in inflammation has been recognized. Galectin-3 has also been shown to directly bind to pathogens and to have various effects on the functions of the cells of the innate immune system. Thanks to these two properties, Galectin-3 participates in several ways in the innate immune response against invading pathogens. Galectin-3 has been proposed to function not only as a pattern-recognition receptor (PRR) but also as a danger-associated molecular pattern (DAMP). In this review, we analyze the various roles that have been assigned to Galectin-3, both as a PRR and as a DAMP, in the context of immune responses against pathogenic microorganisms.

scholarly journals Toll-Like Receptor-Initiated Testicular Innate Immune Responses in Mouse Leydig Cells

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2827-2836 ◽  
Author(s):  
Tao Shang ◽  
Xiaoyan Zhang ◽  
Tao Wang ◽  
Bing Sun ◽  
Tingting Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tyrosine Kinases ◽  
Leydig Cells ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Innate Immune Responses ◽  
Polyinosinic:Polycytidylic Acid ◽  
Tnf Α ◽  
Microbial Infections ◽  
Local Cell

The testis is an immunoprivileged site, where the local cell-initiated testicular innate immune responses play a crucial role in defense against microbial infections. Mechanisms modulating the testicular cell-built defense system remain to be clarified. In this article, we demonstrate that Leydig cells, a major cell population in the testicular interstitium, initiate innate immunity through the activation of Toll-like receptors (TLRs). Several TLRs are expressed in mouse Leydig cells; among these, TLR3 and TLR4 are expressed at relatively high levels compared with other TLR members. Both TLR3 and TLR4 can be activated by their agonists (polyinosinic:polycytidylic acid and lipopolysaccharide) in Leydig cells and subsequently induce the production of inflammatory factors, such as IL-1β, IL-6, TNF-α, and type 1 interferons (IFN) (IFN-α and IFN-β). Notably, the activation of TLR3 and TLR4 suppresses steroidogenesis by Leydig cells. Further, we provide evidence that Axl and Mer receptor tyrosine kinases are expressed in Leydig cells and regulate TLR-mediated innate immune responses negatively. Data presented here describe a novel function of Leydig cells in eliciting testicular innate immune responses that should contribute to the protection of the testis from microbial infections.

scholarly journals Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
C1 Inhibitor ◽  
Serum Samples ◽  
Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

scholarly journals Serum Cytokine Levels in Term and Preterm Deliveries Relating to the Periodontal Health of Mothers: A Pilot Study

2015 ◽  
Vol 4 (2) ◽  
pp. 109-115
Author(s):  
Istvan Gorzo ◽  
Tibor Novák ◽  
Hajnalka Orvos ◽  
Mariann Kovács ◽  
Barbara Bóka ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Birth ◽  
Pilot Study ◽  
Serum Cytokine ◽  
Periodontal Health ◽  
Term Birth ◽  
Periodontal Status ◽  
Tnf Α ◽  
Significant Difference ◽  
Cytokine Levels

ABSTRACT Background The aim of the study was to evaluate serumlevels of interleukin-1, beta (IL-1β) and tumor necrosis factoralpha (TNF-α) at birth and compare the values in case of preterm birth and normal birth groups of mothers considering the mothers’ periodontal status. Materials and methods Blood samples from 81 women (preterm birth, 41 women, and term birth, 40 women) were collected within half an hour of after delivery. Serum levels of IL-1β and TNF-α were measured. Periodontal status was characterized by bleeding on probing (BOP) and probing depth (PD). Results The frequency of BOP differed significantly between preterm and term groups; however, mean PD did not show a significant difference. Serum IL-1β levels were significantly higher in the preterm birth group. The levels TNF-α were slightly bigger in the term birth group, the difference was significant. The rank correlation showed a significant negative relationship between serum IL-1β and TNF-α level and birth weight and the length of pregnancy, and also between BOP frequency and the length of pregnancy. Conclusion Within the limitations of the study, it was found that IL-1β and TNF-α levels were higher when the delivery occurred preterm and the birth weight was smaller; however, a significant increase of cytokines in the serum in connection with maternal periodontal disease was not detected. Periodontics of mothers was not associated with preterm birth in the sample. How to cite this article Radnai M, Novák T, Orvos H, Kovács M, Bóka B, Kele B, Gorzó I. Serum Cytokine Levels in Term and Preterm Deliveries Relating to the Periodontal Health of Mothers: A Pilot Study. Int J Experiment Dent Sci 2015;4(2):109-115.

scholarly journals Pneumolysin is responsible for differential gene expression and modifications in the epigenetic landscape of primary monocyte derived macrophages

2020 ◽  
Author(s):  
J. Cole ◽  
A. Angyal ◽  
R. D. Emes ◽  
T.J. Mitchell ◽  
M.J. Dickman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Epigenetic Modification ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Global Changes ◽  
Innate Immune Responses ◽  
Transcriptional Responses ◽  
Tnf Α

AbstractEpigenetic modifications regulate gene expression in the host response to a diverse range of pathogens. The extent and consequences of epigenetic modification during macrophage responses to Streptococcus pneumoniae, and the role of pneumolysin, a key Streptococcus pneumoniae virulence factor, in influencing these responses, are currently unknown. To investigate this, we infected human monocyte derived macrophages (MDMs) with Streptococcus pneumoniae and addressed whether pneumolysin altered the epigenetic landscape and the associated acute macrophage transcriptional response using a combined transcriptomic and proteomic approach. Transcriptomic analysis identified 503 genes that were differentially expressed in a pneumolysin-dependent manner in these samples. Pathway analysis highlighted the involvement of transcriptional responses to core innate responses to pneumococci including modules associated with metabolic pathways activated in response to infection, oxidative stress responses and NFκB, NOD-like receptor and TNF signalling pathways. Quantitative proteomic analysis confirmed pneumolysin-regulated protein expression, early after bacterial challenge, in representative transcriptional modules associated with innate immune responses. In parallel, quantitative mass spectrometry identified global changes in the relative abundance of histone post translational modifications (PTMs) upon pneumococcal challenge. We identified an increase in the relative abundance of H3K4me1, H4K16ac and a decrease in H3K9me2 and H3K79me2 in a PLY-dependent fashion. We confirmed that pneumolysin blunted early transcriptional responses involving TNF-α and IL-6 expression. Vorinostat, a histone deacetylase inhibitor, similarly downregulated TNF production, reprising the pattern observed with pneumolysin. In conclusion, widespread changes in the macrophage transcriptional response are regulated by pneumolysin and are associated with global changes in histone PTMs. Modulating histone PTMs can reverse pneumolysin-associated transcriptional changes influencing innate immune responses, suggesting that epigenetic modification by pneumolysin plays a role in dampening the innate responses to pneumococci.Author summaryPneumolysin is a toxin that contributes to how Streptococcus pneumoniae, the leading cause of pneumonia, causes disease. In this study, the toxin alters gene expression in immune cells called macrophages, one of the first lines of defence against bacteria at sites of infection. Modulation involved multiple immune responses, including generation of chemical signals coordinating responses in immune cells termed cytokines. In addition, changes were observed in histone proteins that are involved in controlling gene expression in the cell. Pneumolysin reduced early production of the cytokine TNF-α and a medicine vorinostat that modifies these ‘epigenetic’ histone modifications had a similar affect, suggesting epigenetic mechanisms contribute to the ability of pneumolysin to reduce immune responses.

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