Characterization of cytokine/chemokine Profiles of Severe Acute Respiratory Syndrome

Am J Respir Crit Care Med. 2005 Apr 15;171(8):850-7. doi: 10.1164/rccm.200407-857OC. Epub 2005 Jan 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / immunology
  • Chemokine CCL2 / blood
  • Chemokines / blood*
  • Chemokines / genetics
  • Cytokines / blood*
  • Cytokines / genetics
  • Female
  • Gene Expression / physiology
  • Humans
  • Lung / immunology
  • Lung / pathology
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • Lymphoid Tissue / pathology
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • SARS Virus / immunology
  • Severe Acute Respiratory Syndrome / diagnosis
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / pathology
  • Superinfection / immunology
  • Superinfection / pathology

Substances

  • Chemokine CCL2
  • Chemokines
  • Cytokines