interleukin-8 and Myocarditis

Myocardial infarction is associated with an inflammatory response leading to leukocyte recruitment, healing and formation of a scar. Members of the chemokine superfamily are rapidly induced in the infarcted myocardium and may critically regulate the post-infarction inflammatory response. CXCL8/Interleukin (IL)-8 is upregulated in the infarcted area and may induce neutrophil infiltration. In addition, mononuclear cell chemoattractants, such as the CC chemokines CCL2/Monocyte Chemoattractant Protein (MCP)-1, CCL3/Macrophage Inflammatory Protein (MIP)1alpha, and CCL4/MIP-1beta are expressed in the ischemic area, and may regulate monocyte and lymphocyte recruitment. However, chemokines may have additional effects on healing infarcts beyond their leukotactic properties. The CXC chemokine CXCL10/Interferon-y inducible Protein (IP)-10, a potent angiostatic factor with antifibrotic properties, is induced in the infarct and may prevent premature angiogenesis and fibrous tissue deposition, until the infarct is debrided and provisional matrix necessary to support granulation tissue ingrowth is formed. Chemokine induction in the infarct is transient, suggesting that inhibitory mediators (such as transforming growth Factor (TGF)-beta) may be activated suppressing chemokine synthesis and leading to resolution of inflammation and transition to fibrosis. Brief repetitive ischemia in mice also results in chemokine upregulation followed by suppression of chemokine synthesis and interstitial fibrosis, in the absence of myocardial infarction. Chemokine expression may play a role in the pathogenesis of non-infarctive ischemic cardiomyopathy, where early ischemia-induced chemokine expression may be followed by activation of inhibitory mediators that suppress inflammation, but induce fibrosis.

Topics: Animals; Chemokine CCL2; Chemokines; Fibrosis; Humans; Interleukin-8; Myocardial Infarction; Myocardial Reperfusion; Myocarditis; Receptors, Cytokine; Ventricular Remodeling

Human parvovirus B19 infection is occasionally associated with acute lymphocytic myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up clinically, histologically, and immunovirologically. Each infant had B19 virus DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal infection recovered after immunosuppressive therapy. The third infant with possible prenatal infection developed chronic persistent myocarditis associated with persistent B19 virus DNA in the blood. All 3 infants had increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukins -6 and -8. Four newborns with congenital B19 virus infection and 4 infants and children who had postnatally acquired B19 virus infection without myocarditis all had normal levels of these cytokines. These observations suggest that B19 virus infection in infancy causes ALM in some infants and children.

Topics: Acute Disease; Antibodies, Viral; Chronic Disease; Cytokines; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Infant; Interferon-gamma; Interleukin-6; Interleukin-8; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Tumor Necrosis Factor-alpha

Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical benefits. This paradox may indicate that the contribution of inflammation to postoperative sequalae is less than commonly thought or that systemic doses are too low in their local concentration. To test the latter, we evaluated the effects of intramyocardial sevoflurane delivery.. Selective myocardial sevoflurane delivery was performed during aortic cross-clamping in patients undergoing valve surgery (n=11). Results were compared with a control group not receiving sevoflurane (n=10). A reference group (n=5) was added to evaluate the effects of systemic sevoflurane delivery. Paired arterial and myocardial venous blood samples were collected at various time points post-reperfusion. Inflammatory mediators and myocardial cell damage were studied.. Intramyocardial delivery was superior to systemic delivery in attenuation of interleukin-6 and interleukin-8 (-44% and -25%, respectively; both P=0.001). Myocardial and systemic sevoflurane delivery effectively suppressed surgery-related inflammatory responses including postoperative C-reactive protein levels when compared with controls [63 (47-99) (P=0.01) and 58 (56-81) (P=0.04) compared with 107 (79-144) mg litre(-1)]. Sevoflurane treatment did not reduce postoperative troponin T, creatine kinase, and creatine kinase-MB values.. This proof-of-concept study suggests that intramyocardial delivery compared with the systemic delivery of sevoflurane more strongly attenuates the systemic inflammatory response after cardiopulmonary bypass without reducing postoperative markers of myocardial cell damage.. Nederlands Trial Register NTR2089.

Topics: Adult; Aged; Aged, 80 and over; Anesthetics, Inhalation; Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cardiotonic Agents; Female; Humans; Interleukin-6; Interleukin-8; Male; Methyl Ethers; Middle Aged; Mitral Valve; Myocarditis; Postoperative Complications; Prospective Studies; Sevoflurane; Single-Blind Method

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown.. To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection.. This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests.. Patients who died of coronavirus disease 2019.. Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+ cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18.. Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field.. In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.

Topics: Aged; Aged, 80 and over; Autopsy; Cardiovascular Infections; Chemokines; Cohort Studies; COVID-19; Female; Germany; Humans; Incidence; Interferon-gamma; Interleukin-18; Interleukin-6; Interleukin-8; Male; Myocarditis; Myocardium; Pandemics; Peptide Fragments; SARS-CoV-2; Tumor Necrosis Factor-alpha; Viral Load

Cigarette smoking is the leading cause for the initiation and development of cardiovascular disease (CVD). Oxidative stress and inflammatory responses play important roles in the pathophysiological processes of smoking-induced cardiac injury. (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, which is made from Camellia sinensis leaves, has been reported to possess potent anti-oxidant property.. This study aims to investigate whether the antioxidant EGCG could alleviate cigarette smoke medium (CSM)-induced inflammation in human AC16 cardiomyocytes in vitro.. Human AC16 cardiomyocytes were pre-treated with EGCG, N-acetyl-L-cysteine (NAC), or specific inhibitors for 30 min before 4% CSM was added. Supernatant was collected for determination of interleukin (IL)-8 by ELISA and cells were collected for flow cytometry, biochemical assays and Western blot analysis.. EGCG treatment significantly attenuated CSM-induced oxidative stress as evidenced by reducing intracellular and mitochondrial reactive oxygen species (ROS) generations and preventing antioxidant depletion. EGCG treatment reduced CSM-induced inflammatory chemokine interleukin (IL)-8 productions in the supernatant via the inhibition of ERK1/2, p38 MAPK and NF-κB pathways. EGCG treatment further inhibited CSM-induced cell apoptosis.. Taken together, EGCG protected against CSM-induced inflammation and cell apoptosis by attenuating oxidative stress via inhibiting ERK1/2, p38 MAPK, and NF-κB activation in AC16 cardiomyocytes. These findings suggest that EGCG with its antioxidant, anti-inflammatory and anti-apoptotic properties may act as a promising cardioprotective agent against ROS-mediated cardiac injury.

Topics: Antioxidants; Apoptosis; Catechin; Cell Line; Humans; Interleukin-8; MAP Kinase Signaling System; Myocarditis; Myocytes, Cardiac; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Smoking

We hypothesized that postcapillary venules play a central role in the control of the tightness of the coronary system as a whole, particularly under inflammatory conditions. Sandwich cultures of endothelial cells and pericytes of precapillary arteriolar or postcapillary venular origin from human myocardium as models of the respective vascular walls (sandwich cultures of precapillary arteriolar or postcapillary venular origin) were exposed to thrombin and components of the acutely activatable inflammatory system, and their hydraulic conductivity (L(P)) was registered. L(P) of SC-PAO remained low under all conditions (3.24 ± 0.52·10(-8)cm·s(-1)·cmH(2)O(-1)). In contrast, in the venular wall model, PGE(2), platelet-activating factor (PAF), leukotriene B(4) (LTB(4)), IL-6, and IL-8 induced a prompt, concentration-dependent, up to 10-fold increase in L(P) with synergistic support when combined. PAF and LTB(4) released by metabolically cooperating platelets, and polymorphonuclear leucocytes (PMNs) caused selectively venular endothelial cells to contract and to open their clefts widely. This breakdown of the barrier function was preventable and even reversible within 6-8 h by the presence of 50 μM quercetin glucuronide (QG). LTB(4) synthesis was facilitated by biochemical involvement of erythrocytes. Platelets segregated in the arterioles and PMNs in the venules of blood-perfused human myocardium (histological studies on donor hearts refused for heart transplantation). Extrapolating these findings to the coronary microcirculation in vivo would imply that the latter's complex functionality after accumulation of blood borne inflammatory mediators can change rapidly due to selective breakdown of the postcapillary venular barrier. The resulting inflammatory edema and venulo-thrombosis will severely impair myocardial performance. The protection afforded by QG could be of particular relevance in the context of cardiosurgical intervention.

Topics: Actins; Arterioles; Blood Platelets; Blood Proteins; Capillaries; Capillary Permeability; Cells, Cultured; Coronary Circulation; Dinoprostone; Drug Synergism; Endothelial Cells; Erythrocytes; Hemostatics; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukotriene B4; Myocarditis; Pericytes; Platelet Activating Factor; Thrombin; Venules

Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins.. We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P<0.0001 compared with controls).. The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

Topics: Adolescent; Adult; Aged; Animals; Arrhythmias, Cardiac; Autopsy; Biopsy; Cardiomyopathies; Case-Control Studies; Cells, Cultured; Chemokine CCL2; Chemokine CCL4; Child; Desmosomes; Female; gamma Catenin; Humans; Intercellular Junctions; Interleukin-17; Interleukin-6; Interleukin-8; Male; Middle Aged; Models, Animal; Myocarditis; Myocytes, Cardiac; Rats; Rats, Wistar; Sarcoidosis; Signal Transduction; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Right; Young Adult

In the present study, 41 children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with 15 apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside the enzymatic activities of creatine phosphokinase (CPK), CPK-isoenzyme-MB (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24. Electrocardiography and measurements of echocardiographic (Echo) of % fractional shortening of left ventricule (% SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases. All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients of mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis. The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF. In conclusion, cTnI is a specific marker for diagnosis of myoca

Topics: Animals; Antivenins; Child; Creatine Kinase; Creatine Kinase, MB Form; Echocardiography; Electrocardiography; Female; Humans; Interleukin-8; Isoenzymes; L-Lactate Dehydrogenase; Male; Myocarditis; Scorpion Stings; Scorpions; Survival Rate; Troponin I; Ventricular Dysfunction, Left

Diminished cardiac contractility associated with inflammatory infiltration may be mediated by the release of interleukins. To test this hypothesis, we assessed the presence of interleukin and interleukin-receptor mRNAs in non-failing human heart and in endomyocardial biopsies from patients with dilated cardiomyopathy or inflammatory myocarditis. Only those interleukins expressed by non-circulating cells (interleukin-1 beta, -4, and -8) were detected in samples of human heart while interleukins specific for activated leukocytes (interleukins-1 alpha and -2) were not detected in any samples. While interleukin-1-receptor mRNA was present in samples from non-failing hearts and those with idiopathic myopathy, it was absent from patients with inflammatory myocarditis, suggesting receptor mRNA down-regulation.

Topics: Base Sequence; Cardiomyopathies; Cardiomyopathy, Dilated; Interleukin-1; Interleukin-2; Interleukin-4; Interleukin-8; Interleukins; Molecular Sequence Data; Myocarditis; Myocardium; Polymerase Chain Reaction; Receptors, Immunologic; Receptors, Interleukin-1; RNA, Messenger