Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome.

RATIONALE There is currently no optimal treatment or effective drug for severe acute respiratory syndrome (SARS), because the immunopathologic mechanism is poorly understood. OBJECTIVES To explore the immune mechanism underlying the pathogenesis of SARS, we studied the expression profile of cytokines/chemokines in the blood and the immunopathology of the lung and lymphoid tissues. METHODS Fourteen cytokines/chemokines in the blood of 23 patients with SARS were dynamically screened, using a bead-based multiassay system. Reverse transcription-polymerase chain reaction was performed to amplify mRNA. Histopathology of the lung and lymphoid tissues at autopsy was examined, using methods of immunohistochemistry and double immunofluorescence staining. MAIN RESULTS Interferon-inducible protein-10 (IP-10) was markedly elevated in the blood during the early stage of SARS, and remained at a high level until convalescence. Moreover, IP-10 was highly expressed in both lung and lymphoid tissues, where monocyte-macrophage infiltration and depletion of lymphocytes were observed. The levels of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 were concomitantly increased in the blood of the patients with superinfection, and the mRNAs for these cytokines were also increased in lung tissues. CONCLUSIONS Induction of IP-10 is a critical event in the initiation of immune-mediated acute lung injury and lymphocyte apoptosis during the development of SARS. Superinfection after the immune injury is the main cause of death. The prompt elevation of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 is a sign of superinfection, indicating a high risk of death.

[1]  T. Greenough,et al.  What’s new in the renin-angiotensin system? , 2004, Cellular and Molecular Life Sciences CMLS.

[2]  P. Openshaw What does the peripheral blood tell you in SARS? , 2004, Clinical and experimental immunology.

[3]  J. Sung,et al.  Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome , 2004, Clinical and experimental immunology.

[4]  F. Aoki,et al.  Severe Acute Respiratory Syndrome-Related Coronavirus Is Inhibited by Interferon-α , 2004, The Journal of infectious diseases.

[5]  Ton de Jong,et al.  Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. , 2004, Nature medicine.

[6]  J. Peiris,et al.  Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids , 2004, Clinical and experimental immunology.

[7]  J. Peiris,et al.  Re-emergence of fatal human influenza A subtype H5N1 disease , 2004, The Lancet.

[8]  S. Moochhala,et al.  Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome , 2004, The Journal of pathology.

[9]  Hisashi Moriguchi,et al.  Treatment of SARS with human interferons , 2003, The Lancet.

[10]  A. Barton Are clinical negligence and legal action related? , 2003, BMJ : British Medical Journal.

[11]  Shiou-Hwei Yeh,et al.  Microbiologic Characteristics, Serologic Responses, and Clinical Manifestations in Severe Acute Respiratory Syndrome, Taiwan , 2003, Emerging infectious diseases.

[12]  W. Lam,et al.  Management of severe acute respiratory syndrome: the Hong Kong University experience. , 2003, American journal of respiratory and critical care medicine.

[13]  Xin Li,et al.  The clinical pathology of severe acute respiratory syndrome (SARS): a report from China , 2003, The Journal of pathology.

[14]  W. Travis,et al.  Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore , 2003, Human Pathology.

[15]  G. Zeng,et al.  Our strategies for fighting severe acute respiratory syndrome (SARS). , 2003, American journal of respiratory and critical care medicine.

[16]  J. Sung,et al.  Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis , 2003, BMJ : British Medical Journal.

[17]  J. Hoey Updated SARS case definition using laboratory criteria. , 2003, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[18]  K. Holmes SARS coronavirus: a new challenge for prevention and therapy. , 2003, The Journal of clinical investigation.

[19]  Christian Drosten,et al.  Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome , 2003, Science.

[20]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[21]  Yi Guan,et al.  Lung pathology of fatal severe acute respiratory syndrome , 2003, The Lancet.

[22]  B. Williams,et al.  A Viral On/Off Switch for Interferon , 2003, Science.

[23]  K. Holmes,et al.  SARS-associated coronavirus. , 2003, The New England journal of medicine.

[24]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[25]  J. A. Comer,et al.  A novel coronavirus associated with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[26]  B. Rovin,et al.  Chemokines: therapeutic targets for autoimmune and inflammatory renal disease , 2003, Springer Seminars in Immunopathology.

[27]  Geng Li,et al.  Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections , 2003, Archives of disease in childhood. Fetal and neonatal edition.

[28]  Y. Guan,et al.  Coronavirus as a possible cause of severe acute respiratory syndrome , 2003, The Lancet.

[29]  D. Markovitz,et al.  The C-X-C chemokine IP-10 stimulates HIV-1 replication. , 2003, Virology.

[30]  W. Kuis,et al.  Simultaneous Detection of 15 Human Cytokines in a Single Sample of Stimulated Peripheral Blood Mononuclear Cells , 2003, Clinical Diagnostic Laboratory Immunology.

[31]  Jonathan Cohen The immunopathogenesis of sepsis , 2002, Nature.

[32]  Y. Guan,et al.  Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? , 2002, The Lancet.

[33]  T. Lane,et al.  IP-10 and Mig facilitate accumulation of T cells in the virus-infected liver. , 2002, Cellular immunology.

[34]  K. Huber,et al.  Multiple organ failure in patients with cardiogenic shock is associated with high plasma levels of interleukin-6 , 2002, Critical care medicine.

[35]  Klaus Ley,et al.  Chemokines and chemokine receptors in leukocyte trafficking. , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[36]  H. Hartung,et al.  Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. , 2002, Brain : a journal of neurology.

[37]  M. Dziejman,et al.  IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking1 , 2002, The Journal of Immunology.

[38]  T. Rogers,et al.  The effect of X4 and R5 HIV-1 on C, C-C, and C-X-C chemokines during the early stages of infection in human PBMCs. , 2002, Virology.

[39]  T. Ksiazek,et al.  Multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with Ebola virus (reston serotype) * * , 2001, Journal of medical virology.

[40]  H. Keirstead,et al.  Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis1 , 2001, The Journal of Immunology.

[41]  E Lazzeri,et al.  Interferon-inducible protein 10, monokine induced by interferon gamma, and interferon-inducible T-cell alpha chemoattractant are produced by thymic epithelial cells and attract T-cell receptor (TCR) alphabeta+ CD8+ single-positive T cells, TCRgammadelta+ T cells, and natural killer-type cells in hum , 2001, Blood.

[42]  K. Melén,et al.  Inflammatory responses in influenza A virus infection. , 2000, Vaccine.

[43]  I. Julkunen,et al.  Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. , 2000, Virology.

[44]  C. Mackay,et al.  T-cell function and migration. Two sides of the same coin. , 2000, The New England journal of medicine.

[45]  L. Trentin,et al.  CXC chemokines IP-10 and mig expression and direct migration of pulmonary CD8+/CXCR3+ T cells in the lungs of patients with HIV infection and T-cell alveolitis. , 2000, American journal of respiratory and critical care medicine.

[46]  S. Goodbourn,et al.  Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. , 2000, The Journal of general virology.

[47]  M. Buchmeier,et al.  Cutting Edge: The T Cell Chemoattractant IFN-Inducible Protein 10 Is Essential in Host Defense Against Viral-Induced Neurologic Disease1 , 2000, The Journal of Immunology.

[48]  D. Mason,et al.  Double immunofluorescence labelling of routinely processed paraffin sections , 2000, The Journal of pathology.

[49]  D. Sedmak,et al.  Viral Inhibition of Interferon Signal Transduction , 2000, Intervirology.

[50]  Q. Hamid,et al.  The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. , 1999, Journal of immunology.

[51]  A. Luster,et al.  Chemokines--chemotactic cytokines that mediate inflammation. , 1998, The New England journal of medicine.

[52]  L. Koniaris,et al.  Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Chi-kong Li,et al.  Inflammatory cytokine profile in children with severe acute respiratory syndrome. , 2004, Pediatrics.

[54]  R. Brilli,et al.  Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. , 2004, Pediatrics.

[55]  M. V. von Herrath,et al.  Cure of prediabetic mice by viral infections involves lymphocyte recruitment along an IP-10 gradient. , 2004, The Journal of clinical investigation.

[56]  M. Enserink SARS treatment. Interferon shows promise in monkeys. , 2004, Science.

[57]  G. Sen,et al.  Immunology. A viral on/off switch for interferon. , 2003, Science.

[58]  D. Fry,et al.  Multiple organ dysfunction syndrome: past, present and future. , 2000, Surgical infections.

[59]  M Aguet,et al.  The IFN gamma receptor: a paradigm for cytokine receptor signaling. , 1997, Annual review of immunology.