interleukin-8 and Severe-Acute-Respiratory-Syndrome

It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.. Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.. For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1).. Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

Topics: Abdominal Muscles; Animals; Disease Models, Animal; Dogs; Enzyme-Linked Immunosorbent Assay; Inspiratory Reserve Volume; Interleukin-6; Interleukin-8; Lung; Male; Respiration, Artificial; RNA, Messenger; Severe Acute Respiratory Syndrome; Ventilator-Induced Lung Injury

The state of homeostasis links in the children with intestinal colic is represented by the following parameters and clinical characteristics. The data of investigated children's contingent with intestinal colic prevailed by following comorbidities: SARS--12 (18.18% ± 4.78%), protein-energy malnutrition--9 (12.85% ± 3.82%), pneumonia--6 (8.57% ± 3.57%), atopic dermatitis--7 (10.00% ±.3.57%). All children have a next complaints: flatulence (100%), in the 62 children (88.57% ± 3.82%) were identificated frequent regurgitation, in the 48 (80.33%)--hyperbilirubinemia. ALT levels were elevated in 25 children (41%) and 31 (51.66%) children had increased levels of AST. IL8 level were elevated in the 40 children (71.42%). The level of antibodies to elastase was greatly increased in all 56 (100%) children.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Autoantibodies; Colic; Comorbidity; Dermatitis, Atopic; Female; Flatulence; Gastroesophageal Reflux; Humans; Hyperbilirubinemia; Infant; Infant, Newborn; Interleukin-8; Intestines; Male; Malnutrition; Pancreatic Elastase; Pneumonia, Bacterial; Severe Acute Respiratory Syndrome; Ukraine

Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24 h after SARS-CoV infection: (1) IFN-α/β-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS.

Topics: Coronavirus 229E, Human; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Humans; Interleukin-8; Monocytes; Oligonucleotide Array Sequence Analysis; Proteasome Endopeptidase Complex; RNA, Messenger; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-kappaB as central player, whereas expression of type I interferon (IFN)-beta is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI.

Topics: Acute Lung Injury; Aging; Animals; Anti-Inflammatory Agents; Gene Expression; Gene Expression Profiling; Immunity, Innate; Immunohistochemistry; Inflammation; Interferon Type I; Interleukin-8; Macaca; NF-kappa B; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Signal Transduction; Virus Replication

A purified recombinant spike (S) protein was studied for its effect on stimulating human peripheral blood monocyte macrophages (PBMC). We examined inflammatory gene mRNA abundances found in S protein-treated PBMC using gene arrays. We identified differential mRNA abundances of genes with functional properties associated with antiviral (CXCL10) and inflammatory (IL-6 and IL-8) responses. We confirmed cytokine mRNA increases by real-time quantitative(q) RT-PCR or ELISA. We further analyzed the sensitivity and specificity of the prominent IL-8 response. By real-time qRT-PCR, S protein was shown to stimulate IL-8 mRNA accumulation in a dose dependent manner while treatment with E protein did not. Also, titration of S protein-specific production and secretion of IL-8 by ELISA showed that the dose of 5.6nM of S produced a significant increase in IL-8 (p=0.003) compared to mock-treated controls. The increase in IL-8 stimulated by a concentration of 5.6nM of S was comparable to concentrations seen for S protein binding to ACE2 or to neutralizing monoclonal antibody suggesting a physiological relevance. An NF-kappaB inhibitor, TPCK (N-Tosyl-L-Phenylalanine Chloromethyl Ketone) could suppress IL-8 production and secretion in response to S protein in PBMC and THP-1 cells and in HCoV-229E virus-infected PBMC. Activation and translocation of NF-kappaB was shown to occur rapidly following exposure of PBMC or THP-1 cells to S protein using a highly sensitive assay for active nuclear NF-kappaB p65 transcription factor. The results further suggested that released or secreted S protein could activate blood monocytes through recognition by toll-like receptor (TLR)2 ligand.

Topics: Cell Line; Cells, Cultured; Gene Expression; Humans; Interleukin-6; Interleukin-8; Macrophages; Membrane Glycoproteins; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Spike Glycoprotein, Coronavirus; Transcription Factor RelA; Viral Envelope Proteins

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-alpha, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.

Topics: Animals; Antigens, Viral; Communicable Diseases, Emerging; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Genome, Viral; Injections; Injections, Intravenous; Interleukin-12; Interleukin-8; Lung; Lymphoid Tissue; Macaca fascicularis; Macrophages; Macrophages, Alveolar; Male; Models, Animal; Rectum; Reverse Transcriptase Polymerase Chain Reaction; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Trachea; Tumor Necrosis Factor-alpha

Clinical observations and our high-density oligonucleotide microarray results demonstrated increased expression of proinflammatory chemokines after SARS-CoV infection. Here, we investigated the influence of SARS-CoV infection on CXCL8 (interleukin 8) and CXCL10 (interferon-gamma-inducible protein 10) in human intestinal epithelial (Caco2) cells. RT-PCR and ELISA showed time-dependent up-regulation of both chemokines after SARS-CoV infection. Electric mobility shift assay revealed increased DNA binding activity of the cellular transcription factors activator protein 1 (AP-1) and nuclear factor (B (NF-kappaB) in SARS-CoV infected cells. High hydrocortisone concentrations (> or =50 microg/ml) completely prevented increased DNA binding activity of AP-1 and NF-kappaB and inhibited up-regulation of CXCL8 and CXCL10, but did not reduce chemokine expression to basal levels. Ribavirin that does not inhibit SARS-CoV replication in Vero cells inhibited SARS-CoV replication in Caco2 cells at therapeutical concentrations. Hydrocortisone neither influenced SARS-CoV titres alone nor in combination with ribavirin. Our results show that corticosteroids may be of limited benefit in the suppression of chemokine production by SARS-CoV-infected cells.

Topics: Animals; Anti-Inflammatory Agents; Antimetabolites; Cell Line, Tumor; Chemokine CXCL10; Chemokines; Chemokines, CXC; Chlorocebus aethiops; Colonic Neoplasms; DNA; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Hydrocortisone; Inflammation; Interleukin-8; Intestines; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Ribavirin; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Time Factors; Up-Regulation; Vero Cells

Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-alpha were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-beta were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-beta concentrations and SARS severity. The concentrations of IFN-gamma, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-gamma and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cytokines; Female; Humans; Interleukin-1; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Male; Methylprednisolone; Middle Aged; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Although viral replication and overwhelming immune responses are believed to contribute to the progression of severe acute respiratory syndrome (SARS), little is known about the temporal relationship between viral load, ribavirin, proinflammatory cytokines, and clinical progression. We report that ribavirin was not effective in reducing the SARS coronavirus load in 3 of 8 probable cases studied and that elevated levels of interleukin (IL)-6 and IL-8 subsequent to the peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte count during lymphopenia, the peak level of lactate dehydrogenase, and the peak density of pulmonary infiltrates lag further behind the peak viral load by a median of 4, 5, and 3.5 days, respectively. These findings provide important information for therapeutic strategies to treat SARS.

Topics: Adult; Antiviral Agents; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Ribavirin; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Time Factors; Viral Load

To elucidate the mechanism of strong inflammatory response in severe acute respiratory syndrome (SARS) patients.. 24 patients managed with a standard corticosteroid protocol developed by Peking Union Medical College Hospital were followed up for 2 months and their clinical outcomes were documented. Plasma levels of interleukin (IL)-1 beta, IL-2, IL-4, IL-8, IL-10, IL-12 p70, interferon gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) were determined by quantitative ELISA during the course of disease respectively. 12 healthy blood donors were used as normal controls.. All SARS patients had remarkably increased plasma IL-8 concentrations (median 31.23 ng/L) at the onset of disease compared with those of normal controls (6.28 ng/L, P < 0.01). Along with the course of disease IL-8 concentration kept going up and 75% (18/24) patients reached a peak median concentration of 149.65 ng/L (P < 0.01) at the third and fourth weeks. IL-8 came back to normal control levels one month after discharged from hospital. Meanwhile, SARS patients also showed high a TNF alpha level (median 23.12 ng/L) (P < 0.01) at the second week and reached a peak median of 136.35 ng/L (P < 0.05) at the third an fourth weeks. One month after discharged from hospital the plasma TNF alpha concentration fell down to a median of 94.88 ng/L, but it was still much higher than normal controls (3.77 ng/L, P < 0.01).. The SARS-associated coronovirus infection may cause complex cytokine cascade. IL-8 and TNF alpha probably play important roles in mediating strong inflammatory response, which are thought to be responsible for lung injury in SARS patients.

Topics: Adult; Cytokines; Female; Humans; Interleukin-8; Male; Middle Aged; Severe Acute Respiratory Syndrome; Tumor Necrosis Factor-alpha