transforming-growth-factor-beta and Severe-Acute-Respiratory-Syndrome

Topics: Animals; Antiviral Agents; Autophagy; Cell Line; COVID-19; Datasets as Topic; Drug Evaluation, Preclinical; Host-Pathogen Interactions; Humans; Matrix Metalloproteinase Inhibitors; Phosphorylation; Protein Interaction Maps; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Proteome; Proteomics; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Transforming Growth Factor beta; Ubiquitination; Viral Proteins; Viroporin Proteins

Hematological changes in patients with Severe Acute Respiratory Syndrome (SARS) are common and frequently include thrombocytopenia. Using a ELISA method, we found an increase in thrombopoietin (TPO) levels in the plasma of convalesced SARS patients (290+/-53 pg/ml) and active SARS patients (251+/-23 pg/ml) comparing to that from normal control patients (228+/-17 pg/ml). In addition, the plasma from active SARS patients had an inhibitory effect on CFU-MK formation, which could be neutralized by anti-TGF-beta antibodies. In the experiment to determine whether SARS-CoV can directly infect hematopoietic stem cells and megakaryocytic cells, incubation of the cells with SARS-CoV did not show active infection. Our findings of increased TPO levels in the plasma of SARS patients provide a possible explanation for the genesis of thrombocytosis, which frequently develops from thrombocytopenia in SARS patients.

Topics: Antigens, CD34; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Hematopoietic Stem Cells; Humans; Megakaryocytes; Microscopy, Fluorescence; Models, Biological; Regression Analysis; Severe Acute Respiratory Syndrome; Severe acute respiratory syndrome-related coronavirus; Stem Cells; Thrombocytopenia; Thrombopoietin; Transforming Growth Factor beta

The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. To define the dynamics of the immune spectrum in SARS, serum levels of cytokines, chemokines, immunoglobulins, complement and specific antibodies against SARS-associated coronavirus (SARS-CoV) were assayed by enzyme-linked immunosorbent assay (ELISA), and phenotypes of peripheral lymphocytes were analyzed by flow cytometry in 95 SARS-infected patients. Results showed that interleukin (IL)-10 and transforming growth factor beta (TGF-beta) were continuously up-regulated during the entirety of SARS. Regulated on activation normally T cell-expressed and secreted (RANTES) levels were decreased, while monocyte chemoattractant protein-1 (MCP-1) was elevated in acute patients. Immunoglobulins and complement were elevated during the first month of SARS. Both serum-positive rates and titers of specific IgM and IgG antibodies responding to SARS-CoV peaked at days 41-60 from the onset of SARS. CD4+ and CD8+ T lymphocytes decreased significantly in acute-phase. CD3+CD8+CD45RO+ T lymphocytes were decreased by 36.78% in the convalescent patients.. SARS-CoV seemed to elicit effective humoral immunity but inhibited cellular immunity, especially CD8+ memory T lymphocytes over time. Prolonged overproduction of IL-10 and TGF-beta may play an important role in the disease.

Topics: Adolescent; Adult; CD8-Positive T-Lymphocytes; Female; Humans; Interleukin-10; Male; Severe Acute Respiratory Syndrome; Th2 Cells; Time Factors; Transforming Growth Factor beta

Severe acute respiratory syndrome (SARS) has spread to a global pandemic, especially in Asia. The transmission route of SARS has been clarified, but the immunopathogenesis of SARS is unclear. In an age-matched case-control design, we studied immune parameters in 15 SARS patients who were previously healthy. Plasma was harvested for detection of virus load, cytokines, and nitrite/nitrate levels, and blood leukocytes were subjected to flow cytometric analysis of intracellular mitogen-activated protein kinases (MAPKs) in different leukocytes. Patients with SARS had significantly higher IL-8 levels (p = 0.016) in early stage, and higher IL-2 levels (p = 0.039) in late stage than normal controls. Blood TNF-alpha, IL-6, and IL-10, and nitrite/nitrate levels were not significantly elevated. In contrast, TGF-beta and PGE(2) levels were significantly elevated in SARS patients. Five of the 15 SARS patients had detectable coronaviruses in blood, but patients with detectable and undetectable viremia had no different profiles of immune mediators. Flow cytometric analysis of MAPKs activation by phospho-p38 and phospho-p44/42 (extracellular signal-regulated kinase) expression showed that augmented p38 activation (p = 0.044) of CD14 monocytes associated with suppressed p38 activation (p = 0.033) of CD8 lymphocytes was found in SARS patients. These results suggest that regulation of TGF-beta and PGE(2) production and MAPKs activation in different leukocytes may be considered while developing therapeutics for the SARS treatment.

Topics: Adjuvants, Immunologic; Adult; Case-Control Studies; Coronavirus; Cytokines; Dinoprostone; Disease Outbreaks; Gene Expression Regulation, Enzymologic; Humans; Leukocytes; Middle Aged; Mitogen-Activated Protein Kinases; Nitrates; p38 Mitogen-Activated Protein Kinases; Severe Acute Respiratory Syndrome; Transforming Growth Factor beta; Viral Load

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

To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in severe acute respiratory syndrome (SARS) patients.. Sixty-one cases of SARS with positive antibodies to SARS coronavirus (SARS-CoV) were classified into the following categories: initial stage (3 - 7 days), peak stage (8 - 14 days), and remission and recovery stage (15 - 27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-alpha and TGF-beta 1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases.. The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages (P < 0.01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage (P < 0.05). And it was more significantly higher in remission and recovery stage than in peak stage (P < 0.01). The mean concentrations of IL-16 and TNF-alpha in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage (P < 0.01). SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage (P < 0.01), but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses (P < 0.05). The mean concentration of serum TGF-beta1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-beta1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group (P < 0.01).. Most proinflammatory cytokines and TGF-beta 1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.

Topics: Adolescent; Adult; Female; Humans; Interleukins; Male; Middle Aged; Severe Acute Respiratory Syndrome; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in severe acute respiratory syndrome (SARS).. Sixty-one cases of SARS were classified into the following categories according to the duration from the onset of illness to the time blood was drawn: 3-7 day group, 8-14 day group and over 14 day group. Forty-four healthy individuals served as the control. Serum levels of ILs, TNF-alpha and TGF-beta1 were measured in all cases. Serum antibodies to SARS-coronavirus (SARS-CoV) were measured only in SARS cases.. The mean concentration of serum IL-6 in SARS patients did not differ from the control group in 3-7 day group and 8-14 day group, but became significantly higher in over 14 day group as compared to the control group, 3-7 day group and 8-14 day group (P < 0.01). The mean concentration of serum IL-8 in SARS patients did not differ from the control group in 3-7 day group, were significantly higher than the control group in 8-14 days group and in over 14 day group (P < 0.05) and significantly higher in over 14 day group than in 3-7 day group and 8-14 day group (P < 0.01). The mean concentration of IL-16 and TNF-alpha in all groups of SARS was higher than that of the control group, but it was the highest in over 14 day group (P < 0.01). SARS patients experienced higher concentration of serum IL-13 as compared to controls in 3-7 day group (P < 0.01), but it returned to normal levels in 8-14 day group and the over 14 day group. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all groups of SARS patients (P < 0.05); The mean concentration of TGF-beta1 in all groups of SARS patients was higher than that of the control group. Although TGF-beta1 in sera decreased in over 14 day group, the average was still higher than that of the control group (P < 0.01).. Proinflammatory cytokines and TGF-beta1 were elevated during the early phase of SARS, a phenomenon which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during the whole disease course. It suggested that the immune state of SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide us with a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.

Topics: Adolescent; Adult; Aged; Cytokines; Female; Humans; Interleukins; Male; Middle Aged; Severe Acute Respiratory Syndrome; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha