scholarly journals Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction.

1975 ◽  
Vol 141 (2) ◽  
pp. 346-359 ◽  
Author(s):  
H M Wisniewski ◽  
B R Bloom
Keyword(s):  
Mononuclear Cells ◽  
Demyelinating Disease ◽  
Inflammatory Cells ◽  
Polymorphonuclear Cells ◽  
Inflammatory Reactions ◽  
Purified Protein Derivative ◽  
Primary Demyelination ◽  
Tissue Antigens ◽  
A Cell ◽  
Constant Feature

Primary demyelination occurs in a variety of human and experimental diseases known to be associated with the presence of inflammatory cells. However, the mechanism of demyelination remains unclear. The possibility that myelin can be damaged as a nonspecific consequence of a specific delayed type of hypersensitivity reaction directed at nonnervous tissue antigens was investigated. Guinea pigs were sensitized to tuberculin with Freund's complete adjuvant, and were challenged in the central and peripheral nervous system either with live or killed sonicated tubercle bacilli, Old Tuberculin, or tuberculin purified protein derivative (PPD). Local inflammatory reactions were invariably produced and primary demyelination was a constant feature of the lesions. The morphological picture was rather similar to that observed in human neurotuberculosis and early tuberculoid leprosy, and in experimental allergic encephalomyelitis and distemper encephalitis in animals. The infiltrates consisted predominantly of mononuclear cells with some polymorphonuclear cells as well. Vesicular disruption of the myelin sheath in the immediate vicinity of the inflammatory cells and stripping of the myelin lamellae by the histiocytes without axonal damage were the leading features of the lesion. The results indicate that cell-mediated immune reactions to a variety of nonbrain antigens could be responsible for a component of the demyelination seen in some inflammatory demyelinating conditions, and suggest that this system may serve as a useful model for studying the immunopathology of demyelinating disease.

scholarly journals Il6/Sil6R Regulates Tnfα-Inflammatory Response In Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα or IL6 and sIL6R for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cicloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assesed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results IL6/sIL6R stimulation of TNFα treated SF cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals Concurrent helminthosis engendered gastroenteritis in a leopard Panthera pardus

2019 ◽  
Vol 56 (4) ◽  
pp. 323-328
Author(s):  
R. Kumar ◽  
A. D. Moudgil ◽  
A. Sharma ◽  
R. Sharma ◽  
R. Masand ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Toxocara Canis ◽  
Intestinal Content ◽  
Detailed Examination ◽  
Pathological Examination ◽  
Polymorphonuclear Cells ◽  
Panthera Pardus ◽  
Parasitic Gastroenteritis ◽  
Present Case Study

SummaryThe necropsy of a leopard (Panthera pardus), succumbed to a chronic ailment exhibited a mixed parasitic gastroenteritis. Gross internal examination of carcass revealed the presence of round and tapeworms in the stomach and intestines with diffuse catarrhal and hemorrhagic gastroenteritis. The detailed examination of the intestinal content revealed the presence of Toxocara canis and Spirometra species eggs. Also, the gross morphological investigation of round and tapeworms approved the presence of both species. Histo-pathological examination showed sloughing of intestinal epithelium, hemorrhages, and ulcerative areas with the infiltration of polymorphonuclear cells admixed with mononuclear cells. Lungs revealed the accumulation of eosinophilic edematous fl uid in the alveolar spaces along with inflammatory cells. These parasites are pathogenic to precious wild felids and often pose a threat of zoonotic transmission due to spill-over infections. The present case study is an attempt to put on record a case of parasitic gastroenteritis in a captive leopard.

scholarly journals Inflammation in rats born to mothers treated with dexamethasone 15cH during pregnancy: an immunohistochemical study

2021 ◽  
Vol 10 (35) ◽  
pp. 70-70
Author(s):  
Thayná Neves Cardoso ◽  
Leoni Villano Bonamin
Keyword(s):  
Mast Cell ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Mast Cell Degranulation ◽  
Polymorphonuclear Cells ◽  
Cellular Events ◽  
Detailed Assessment ◽  
Hematoxylin Eosin ◽  
Arteriolar Diameter

In previous studies, we observed that rats born to mothers treated with dexamethasone 15CH (10-33M) had a higher level of mast cell degranulation and greater arteriolar dilation after the exposure of an inflammatory stimulus, suggesting the possibility of vertical transmission of the effects of ultra-diluted substances between mother and offspring. In this study, a more detailed assessment of the cellular events in acute inflammation was made using techniques of immunohistochemistry. The identification of adhesion molecules expression was made by the markers: anti-CD54 (ICAM-1) and anti-CD18 (β2-Integrin). The identification of inflammatory cells was performed by the markers anti-MAC387 (mononuclear cells) and anti-CD163 (active macrophages). Polymorphonuclear cells were identified by hematoxylin-eosin staining. The number of labeled cells per field was recorded, except for the anti-CD54 marker, whose intensity of staining on the endothelial cells was defined by scores assigned by two independent observers. The results point toward to an up regulation of the whole inflammatory process in rats born to mothers treated with dexamethasone 15CH during pregnancy. This conclusion is justified by the following statistically significant (p≤0.05) findings: a) bigger mast cell degranulation and increased of arteriolar diameter; b) increased migration of polymorphonuclear cells in relation to the mononuclear cells; c) earlier expression of CD163 in monocytes, d) higher level of adhesion molecules expression.

scholarly journals IL6/sIL6R regulates TNFα-inflammatory response in synovial fibroblasts through modulation of transcriptional and post-transcriptional mechanisms

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes ◽  
Two Factors

Abstract Introduction The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results The stimulation of SF with IL6/sIL6R and TNFα, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals IL6/sIL6R REGULATES TNFα-INFLAMMATORY RESPONSE IN SYNOVIAL FIBROBLASTS THROUGH MODULATION OF TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL MECHANISMS

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value <0.05 was considered statistically significant. Results: The stimulation of SF with IL6/sIL6R and TNFa, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals IL6/sIL6R Regulates Tnfa-Inflammatory Response in Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

2020 ◽  
Author(s):  
Alvaro Valin ◽  
Manuel J. Del Rey ◽  
Cristina Municio ◽  
Alicia Usategui ◽  
Marina Romero ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
De Novo ◽  
Inflammatory Cells ◽  
Synovial Fibroblasts ◽  
Matrix Metalloproteases ◽  
P Value ◽  
Polymorphonuclear Cells ◽  
Expression Of Genes

Abstract Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF.Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value <0.05 was considered statistically significant.Results: The stimulation of SF with IL6/sIL6R and TNFa, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.

scholarly journals A Protein Critical for a Theiler’s Virus-Induced Immune System-Mediated Demyelinating Disease Has a Cell Type-Specific Antiapoptotic Effect and a Key Role in Virus Persistence

1998 ◽  
Vol 72 (11) ◽  
pp. 8605-8612 ◽  
Author(s):  
Ghanashyam D. Ghadge ◽  
Li Ma ◽  
Shigeru Sato ◽  
Jong Kim ◽  
Raymond P. Roos
Keyword(s):  
Immune System ◽  
Demyelinating Disease ◽  
Central Nervous System Infection ◽  
Inflammatory Cells ◽  
Virus Persistence ◽  
Reading Frame ◽  
Virus Clearance ◽  
Encephalomyelitis Virus ◽  
A Cell ◽  
Apoptotic Activity

ABSTRACT TO subgroup strains of Theiler’s murine encephalomyelitis virus (TMEV) induce a persistent central nervous system infection and demyelinating disease in mice. This disease serves as an experimental model of multiple sclerosis (MS) because the two diseases have similar inflammatory white matter pathologies and because the immune system appears to mediate demyelination in both processes. We previously reported (H. H. Chen, W. P. Wong, L. Zhang, P. L. Ward, and R. P. Roos, Nat. Med. 1:927–931, 1995) that TO subgroup strains use an alternative initiation codon (in addition to the AUG used to synthesize the picornavirus polyprotein from one long open reading frame) to translate L*, a novel protein that is out of frame with the polyprotein and which plays a key role in the demyelinating disease. We now demonstrate that L* has antiapoptotic activity in macrophage cells and is critical for virus persistence. The antiapoptotic action of L* as well as the differential translation of L* and virion capsid proteins may foster virus persistence in macrophages and interfere with virus clearance. The regulation of apoptotic activity in inflammatory cells may be important in the pathogenesis of TMEV-induced demyelinating disease as well as MS.

scholarly journals Anti-inflammatory genes in PBMCs post-spontaneous intracerebral hemorrhage

2021 ◽  
Vol 12 (1) ◽  
pp. 58-66
Author(s):  
Doan Nguyen ◽  
Vi Tran ◽  
Alireza Shirazian ◽  
Cruz Velasco-Gonzalez ◽  
Ifeanyi Iwuchukwu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Negative Correlation ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Favorable Outcome ◽  
Hospital Length Of Stay ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Hematoma Volume ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory

Abstract Background Neuroinflammation is important in the pathophysiology of spontaneous intracerebral hemorrhage (ICH) and peripheral inflammatory cells play a role in the clinical evolution and outcome. Methodology Blood samples from ICH patients (n = 20) were collected at admission for 5 consecutive days for peripheral blood mononuclear cells (PBMCs). Frozen PBMCs were used for real-time PCR using Taqman probes (NFKB1, SOD1, PPARG, IL10, NFE2L2, and REL) and normalized to GAPDH. Data on hospital length of stay and modified Rankin score (MRS) were collected with 90-day MRS ≤ 3 as favorable outcome. Statistical analysis of clinical characteristics to temporal gene expression from early to delayed timepoints was compared for MRS groups (favorable vs unfavorable) and hematoma volume. Principle findings and results IL10, SOD1, and REL expression were significantly higher at delayed timepoints in PBMCs of ICH patients with favorable outcome. PPARG and REL increased between timepoints in patients with favorable outcome. NFKB1 expression was not sustained, but significantly decreased from higher levels at early onset in patients with unfavorable outcome. IL10 expression showed a negative correlation in patients with high hematoma volume (>30 mL). Conclusions and significance Anti-inflammatory, pro-survival regulators were highly expressed at delayed time points in ICH patients with a favorable outcome, and IL10 expression showed a negative correlation to high hematoma volume.

scholarly journals Endoscopic and Histopathological Findings of the Esophagus, Stomach, and Duodenum in Patients with Crohn’s Disease from a Reference Center in Bahia, Brazil

2021 ◽  
Vol 11 (2) ◽  
pp. 374-385
Author(s):  
Andrea Maia Pimentel ◽  
Luiz Antônio Rodrigues de Freitas ◽  
Rita de Cássia Reis Cruz ◽  
Isaac Neri de Novais Silva ◽  
Laíla Damasceno Andrade ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Erosive Esophagitis ◽  
Gastric Body ◽  
Polymorphonuclear Cells ◽  
Cross Sectional ◽  
Histopathological Findings ◽  
Focally Enhanced Gastritis ◽  
H Pylori

(1) The aim of the present study was to describe the endoscopic and histopathological findings in the esophagus, stomach, and duodenum in patients with Crohn’s disease. (2) Methods: This was a cross-sectional study that included patients receiving treatment from the inflammatory bowel disease outpatient clinic. Esophagogastroduodenoscopies with biopsies of the stomach and proximal duodenum were performed. Presence of Helicobacter pylori bacteria was assessed by Giemsa staining. (3) Results: We included 58 patients. Erosive esophagitis was identified in 25 patients (43.1%), gastritis was diagnosed in 32 patients (55.2%) and erosive duodenitis was found in eight (13.8%). The most frequent histopathological finding in the H. pylori-positive group was increased inflammatory activity in the gastric body and antrum, with a predominance of mononuclear and polymorphonuclear cells. In turn, the most frequent finding in the H. pylori-negative group was chronic inflammation with predominance of mononuclear cells. Focally enhanced gastritis was identified in four patients (6.9%), all of whom were negative for H. pylori. Granulomas were not observed. H. pylori infection was present in 19 patients (32.8%). (4) Conclusions: Nonspecific endoscopic and histological findings were frequent in patients with Crohn’s disease. Focally enhanced gastritis was uncommon and observed only in H. pylori-negative patients. The time from the diagnosis, patient age, and therapy in use may have influenced the nondetection of epithelioid granuloma.

scholarly journals Post-operative septic arthritis after arthroscopy: modern diagnostic and therapeutic concepts

2021 ◽  
Author(s):  
Andreas Voss ◽  
Christian G. Pfeifer ◽  
Maximilian Kerschbaum ◽  
Markus Rupp ◽  
Peter Angele ◽  
...  
Keyword(s):  
Septic Arthritis ◽  
Cell Count ◽  
Clinical Symptoms ◽  
Arthroscopic Surgery ◽  
Polymorphonuclear Cells ◽  
Level Of Evidence ◽  
Therapeutic Concepts ◽  
A Cell ◽  
Low Incidence ◽  
Joint Puncture

Abstract Purpose Septic arthritis is a significant complication following arthroscopic surgery, with an estimated overall incidence of less than 1%. Despite the low incidence, an appropriate diagnostic and therapeutic pathway is required to avoid serious long-term consequences, eradicate the infection, and ensure good treatment outcomes. The aim of this current review article is to summarize evidence-based literature regarding diagnostic and therapeutic options of post-operative septic arthritis after arthroscopy. Methods Through a literature review, up-to-date treatment algorithms and therapies have been identified. Additionally, a supportive new algorithm is proposed for diagnosis and treatment of suspected septic arthritis following arthroscopic intervention. Results A major challenge in diagnostics is the differentiation of the post-operative status between a non-infected hyperinflammatory joint versus septic arthritis, due to clinical symptoms, (e.g., rubor, calor, or tumor) can appear identical. Therefore, joint puncture for microbiological evaluation, especially for fast leukocyte cell-count diagnostics, is advocated. A cell count of more than 20.000 leukocyte/µl with more than 70% of polymorphonuclear cells is the generally accepted threshold for septic arthritis. Conclusion The therapy is based on arthroscopic or open surgical debridement for synovectomy and irrigation of the joint, in combination with an adequate antibiotic therapy for 6–12 weeks. Removal of indwelling hardware, such as interference screws for ACL repair or anchors for rotator cuff repair, is recommended in chronic cases. Level of evidence IV.

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