scholarly journals Level of cellular reactivity of organism and extent of intoxication severity in patients with acute and exacerbation of chronic pancreatitis depending on genes polymorphism CFTR, PRSS1, IL-4 and TNF-α

2017 ◽  
Vol 35 (1) ◽  
pp. 21-27 ◽  
Author(s):  
S. I. Ivashchuk ◽  
L. P. Sydorchuk ◽  
O. M. Korovenkova
Keyword(s):  
Chronic Pancreatitis ◽  
Immune System ◽  
Clinical Course ◽  
Allergic Reactions ◽  
Tnf Α ◽  
Gène Cftr

The level of cellular reactivity of organism and extent of intoxication severity depending on genes polymorphism CFTR (ΔF508, rs 113993960), PRSS1 (R122H, rs 111033565), IL-4 (C-590T, rs 2243250) and TNF-α (G-308A, rs 1800629) were investigated in 123 patients with acute and exacerbation of chronic pancreatitis (edematous form). It has been established that higher level of cellular reactivity by 20,96% (р<0,05) and endointoxication occurs in the carriers of NN-genotype of the gene CFTR, thus showing less favourable clinical course of pancreatitis. The higher degree of exo- and endointoxication formation has been observed in the carriers of GA-genotype of the gene PRSS1 on the background of considerable limitation of allergic reactions development. In the carriers of TT-genotype of the gene IL-4 there is the most serious degree of intoxication on the background of hyporeactivity and maximum limitation of immune system hypersensitivity to exo- and endotoxins.

scholarly journals Bacillus anthracis Spores Stimulate Cytokine and Chemokine Innate Immune Responses in Human Alveolar Macrophages through Multiple Mitogen-Activated Protein Kinase Pathways

2006 ◽  
Vol 74 (8) ◽  
pp. 4430-4438 ◽  
Author(s):  
Kaushik Chakrabarty ◽  
Wenxin Wu ◽  
J. Leland Booth ◽  
Elizabeth S. Duggan ◽  
K. Mark Coggeshall ◽  
...  
Keyword(s):  
Immune System ◽  
Bacillus Anthracis ◽  
Alveolar Macrophages ◽  
Innate Immune System ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Tnf Α ◽  
Human Alveolar Macrophages ◽  
Mitogen Activated Protein ◽  
Multiple Signaling

ABSTRACT Contact with the human alveolar macrophage plays a key role in the innate immune response to Bacillus anthracis spores. Because there is a significant delay between the initial contact of the spore with the host and clinical evidence of disease, there appears to be temporary containment of the pathogen by the innate immune system. Therefore, the early macrophage response to Bacillus anthracis exposure is important in understanding the pathogenesis of this disease. In this paper, we studied the initial events after exposure to spores, beginning with the rapid internalization of spores by the macrophages. Spore exposure rapidly activated the mitogen-activated protein kinase signaling pathways extracellular signal-regulated kinase, c-Jun-NH2-terminal kinase, and p38. This was followed by the transcriptional activation of cytokine and primarily monocyte chemokine genes as determined by RNase protection assays. Transcriptional induction is reflected at the translational level, as interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) cytokine protein levels were markedly elevated as determined by enzyme-linked immunosorbent assay. Induction of IL-6 and TNF-α, and, to a lesser extent, IL-1α and IL-1β, was partially inhibited by the blockade of individual mitogen-activated protein kinases, while the complete inhibition of cytokine induction was achieved when multiple signaling pathway inhibitors were used. Taken together, these data clearly show activation of the innate immune system in human alveolar macrophages by Bacillus anthracis spores. The data also show that multiple signaling pathways are involved in this cytokine response. This report is the first comprehensive examination of this process in primary human alveolar macrophages.

scholarly journals Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 Cytokine Storm

2020 ◽  
Vol 9 (7) ◽  
pp. 2095 ◽  
Author(s):  
Mattia Vinciguerra ◽  
Silvia Romiti ◽  
Khalil Fattouch ◽  
Antonio De Bellis ◽  
Ernesto Greco
Keyword(s):  
Immune System ◽  
Viral Replication ◽  
Multiorgan Failure ◽  
Severe Infection ◽  
Adverse Outcomes ◽  
Alveolar Cells ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Plasmatic Concentration

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) outbreak is a public health emergency affecting different regions around the world. The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection varies from complete absence of symptomatology to more aggressive symptoms, characterized by sudden acute respiratory distress syndrome (ARDS), multiorgan failure, and sepsis, requiring treatment in intensive care unit (ICU). It is not still clear why the immune system is not able to efficiently suppress viral replication in a small percentage of patients. It has been documented as pathological conditions affecting the cardiovascular system, strongly associated to atherosclerotic progression, such as heart failure (HF), coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM), could serve as predictive factors for severity and susceptibility during Sars-CoV-2 infection. Atherosclerotic progression, as a chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory patterns, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results reported in severe COVID-19 infections, we hypothesized a pathogenetic correlation. Atherosclerosis may be an ideal pathogenetic substrate for high viral replication ability, leading to adverse outcomes, as reported in patients with cardiovascular factors. The level of atherosclerotic progression may affect a different degree of severe infection; in a vicious circle, feeding itself, Sars-CoV-2 may exacerbate atherosclerotic evolution due to excessive and aberrant plasmatic concentration of cytokines.

scholarly journals The clinical course of chronic pancreatitis associated with lipid disturbances in children

2012 ◽  
Vol 5 ◽  
pp. 286-290
Author(s):  
Grzegorz Oracz ◽  
Jarosław Kierkuś ◽  
Jerzy Socha ◽  
Józef Ryżko
Keyword(s):  
Chronic Pancreatitis ◽  
Clinical Course

scholarly journals Epileptogenesis due to glia-mediated synaptic scaling

2008 ◽  
Vol 6 (37) ◽  
pp. 655-668 ◽  
Author(s):  
Cristina Savin ◽  
Jochen Triesch ◽  
Michael Meyer-Hermann
Keyword(s):  
Immune System ◽  
Neuronal Activity ◽  
Activity Patterns ◽  
Brain Inflammation ◽  
Network Activity ◽  
Homeostatic Regulation ◽  
Synaptic Scaling ◽  
Tnf Α ◽  
Factor Α ◽  
Potential Interactions

Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.

scholarly journals Tanshinone IIA Attenuates Chronic PancreatitisInduced Pain in Rats via Downregulation of HMGB1 and TRL4 Expression in the Spinal Cord

2015 ◽  
Vol 18;4 (4;18) ◽  
pp. E615-E628
Author(s):  
Lei Chen
Keyword(s):  
Chronic Pancreatitis ◽  
Western Blot ◽  
Proinflammatory Cytokine ◽  
Mechanical Allodynia ◽  
Tanshinone Iia ◽  
Trinitrobenzene Sulfonic Acid ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Tnf Α ◽  
Dose Dependent

Background: Chronic pancreatitis (CP) is a long-standing inflammation of the exocrine pancreas, which typically results in severe and constant abdominal pain. Previous studies on the mechanisms underlying CP-induced pain have primarily focused on the peripheral nociceptive system. A role for a central mechanism in the mediation or modulation of abdominal pain is largely unknown. Tanshinone IIA (TSN IIA), an active component of the traditional Chinese medicine Danshen, exhibits anti-inflammatory properties via downregulation of the expression of high-mobility group protein B1 (HMGB1), a late proinflammatory cytokine. HMGB1 binds and activates toll-like receptor 4 (TLR4) to induce spinal astrocyte activation and proinflammatory cytokine release in neuropathic pain. Objective: In this study, we investigated the effect of TSN IIA on pain responses in rats with trinitrobenzene sulfonic acid (TNBS)-induced CP. The roles of central mechanisms in the mediation or modulation of CP were also investigated. Study Design: A randomized, double-blind, placebo-controlled animal trial. Methods: CP was induced in rats by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Pancreatic histopathological changes were characterized with semi-quantitative scores. The abdomen nociceptive behaviors were assessed with von Frey filaments. The effects of intraperitoneally administered TSN IIA on CP-induced mechanical allodynia were tested. The spinal protein expression of HMGB1 was determined by western blot. The spinal mRNA and protein expression of proinflammatory cytokines IL-1β, TNF-α, and IL-6 were determined by RT-PCR and western blot, respectively. The spinal expression of the HMGB1 receptor TRL4 and the astrocyte activation marker glial fibrillary acidic protein (GFAP) were determined by western blot or immunohistological staining after intraperitoneal injection of TSN IIA or intrathecal administration of a neutralizing anti-HMGB1 antibody. Results: TNBS infusion resulted in pancreatic histopathological changes of chronic pancreatitis and mechanical allodynia in rats. TSN IIA significantly attenuated TNBS-induced mechanical allodynia in a dose-dependent manner. TNBS significantly increased the spinal expression of HMGB1 and proinflammatory cytokines IL-1β, TNF-α, and IL-6. These TNBS-induced changes were significantly inhibited by TSN IIA in a dose-dependent manner. Furthermore, TSN IIA, but not the neutralizing anti-HMGB1 antibody, significantly inhibited TNBS-induced spinal TLR4 and GFAP expression. Limitations: In addition to TLR4, HMGB1 can also bind to toll-like receptor-2 (TLR2) and the receptor for advanced glycation end products (RAGE). Additional studies are warranted to ascertain whether HMGB1 contributes to CP-induced pain through activation of these receptors. Conclusions: Our results suggest that spinal HMGB1 contributes to the development of CPinduced pain and can potentially be a therapeutic target. TSN IIA attenuates CP-induced pain via downregulation of spinal HMGB1 and TRL4 expression. Therefore, TSN IIA may be a potential anti-nociceptive drug for the treatment of CP-induced pain. Key words: Chronic pancreatitis, HMGB1, proinflammatory cytokine, Tanshinone IIA, spinal cord, astrocyte, TLR4

scholarly journals Plasma levels of melatonin, certain cytokines and placental growth factor at non-pharmacological correction of pineal function in pregnant women with intrauterine growth restriction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
A. Berbets ◽  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Pineal Gland ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Placental Growth Factor ◽  
Placental Insufficiency ◽  
Tnf Α ◽  
Anti Inflammatory

The pineal gland produces the important hormone melatonin, the level of which in the blood of pregnant women decreases in case of placental insufficiency. The effect of dysfunction of the pineal gland on the immune system of pregnant women and on the angiogenic activity of the placenta during pregnancy remains insufficiently studied. Objective: to establish the effect of our method of non-drug correction of function of pineal gland on the state of the cytokine part of the immune system and on the synthesis of placental growth factor (PlGF) in pregnant women with placental insufficiency manifesting as fetal intrauterine growth restriction (IUGR). Material and methods. 46 pregnant women with IUGR at 30-36 weeks of gestation were examined. The group was divided into two subgroups: with non-drug correction of the pineal gland function (n = 25) and without correction (n = 21). The method of correction included a set of measures of following of lighting regimen, activity and sleep for 14 days. The control group consisted of 20 women with uncomplicated pregnancy. Levels of melatonin, PlGF, TNF-α, IL-1β, IL-6, IL-4, IL-10 were determined in the venous blood by enzyme-linked immunosorbent assay. Results. It was established that the concentration of melatonin in the blood of pregnant women with IUGR was significantly reduced, as well as the concentration of PlGF (p < 0.01). Significant changes were also found in pregnant women with placental insufficiency, namely, increased concentrations of proinflammatory cytokines, such as TNF-α (p < 0.05), IL-1-β (p < 0.001) and IL-6 (p < 0.05), comparing to healthy pregnant women. Also, in the group of pregnant women with IUGR the levels of anti-inflammatory cytokines IL-4 (p <0.001) and IL-10 (p < 0.001) were elevated in comparison to the control group. After application of the developed complex of non-drug correction of pineal gland function, the concentration of melatonin in the blood of pregnant women in the subgroup of correction increased significantly, comparing to the subgroup without correction (p < 0.001), as well as the level of PlGF (p < 0.05). Also, significantly lower levels of proinflammatory cytokines TNF-α, IL-1-β and IL-6 were observed in pregnant women in the subgroup of correction (p < 0.01). Regarding anti-inflammatory cytokines, under the influence of the developed complex of measures there was a decrease in the level of IL-4 and an increase in the level of IL-10 (p < 0.01). Conclusions. When the measures, aimed at non-drug correction of function of pineal gland, are applied in pregnant women with placental insufficiency, manifested as IUGR, the following changes are observed: increased of plasma levels of melatonin and placental growth factor, decreased of levels of proinflammatory cytokines. We suggest that the pineal gland exerts its effect on the immune system through melatonin, which moderates the activity of pro- and anti-inflammatory cytokines, thereby reducing the influence of inflammation on placental tissue, what results in increasing of concentrations of placental growth factor in the blood of pregnant women.

scholarly journals Differential Activation of Innate Immune Responses by Adenovirus and Adeno-Associated Virus Vectors

2002 ◽  
Vol 76 (9) ◽  
pp. 4580-4590 ◽  
Author(s):  
Anne-Kathrin Zaiss ◽  
Qiang Liu ◽  
Gloria P. Bowen ◽  
Norman C. W. Wong ◽  
Jeffrey S. Bartlett ◽  
...  
Keyword(s):  
Immune System ◽  
Intravenous Administration ◽  
Innate Immune System ◽  
Innate Immune ◽  
Target Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adeno Associated Virus ◽  
Tnf Α ◽  
Adenovirus Vectors

ABSTRACT Adenovirus vectors induce acute inflammation of infected tissues due to activation of the innate immune system and expression of numerous chemokines and cytokines in transduced target cells. In contrast, adeno-associated virus (AAV) vectors are not associated with significant inflammation experimentally or clinically. We tested the ability of AAV vectors to induce the expression of chemokines in vitro and to activate the innate immune system in vivo. In human HeLa cells and murine renal epithelium-derived cells (REC cells) the adenovirus vector AdlacZ induced the expression of multiple inflammatory chemokines including RANTES, interferon-inducible protein 10 (IP-10), interleukin-8 (IL-8), MIP-1β, and MIP-2 in a dose-dependent manner. The use of AAVlacZ did not induce the expression of these chemokines above baseline levels despite 40-fold-greater titers than AdlacZ and greater amounts of intracellular AAVlacZ genomes according to Southern and slot blot analysis. This finding confirmed that the lack of AAVlacZ induction of chemokine was not due to reduced transduction. In DBA/2 mice, the intravenous administration of 2.5 × 1011 particles of AAVlacZ resulted in the rapid induction of liver tumor necrosis factor alpha (TNF-α), RANTES, IP-10, MIP-1β, MCP-1, and MIP-2 mRNAs. However, 6 h following injection, chemokine mRNA levels returned to baseline. As expected, administration of 10-fold less AdlacZ caused an induction of liver TNF-α and chemokine mRNAs that persisted for more than 24 h posttransduction. Whereas intravenous administration of 2.5 × 1011 particles of AAVlacZ triggered a transient infiltration of neutrophils and CD11b+ cells into liver, this response stood in contrast to widespread inflammation and toxicity induced by AdlacZ. Kupffer cell depletion abolished AAVlacZ but not AdlacZ-induced chemokine expression and neutrophil infiltration. In summary, these results show that AAV vectors activate the innate immune system to a lesser extent than do adenovirus vectors and offer a possible explanation for the reduced inflammatory properties of AAV compared to adenovirus vectors.

Variations in time of serum pancreatic enzyme levels in chronic pancreatitis and clinical course of the disease

1991 ◽  
Vol 8 (4) ◽  
Author(s):  
Luigi Benini ◽  
Silvio Caliari ◽  
Bruna Vaona ◽  
Giorgio Brocco ◽  
Rocco Micciolo ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Clinical Course ◽  
Pancreatic Enzyme
Sign in / Sign up

Export Citation Format

Share Document