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T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis.

Abstract
Exposure to immunosuppressive environmental contaminants is a possible contributing factor to increased occurrence of viral respiratory diseases. The objective of this study was to test the hypothesis that the trichothecene mycotoxin T-2 toxin (T-2), a frequent food contaminant, alters host resistance to lung infection by reovirus, a model respiratory virus. Balb/c mice (4 week old) were treated intraperitoneally with T-2 toxin (1.75 mg/kg bw) or saline vehicle and then intranasally instilled 2 h later with 10(7) plaque forming unit (PFU) of reovirus, strain Lang (T1/L) or saline vehicle. At 10 days post-instillation (PI), both virus plaque-forming responses and reovirus L2 gene expression were 10-fold higher in lungs of T-2-treated mice compared to controls. No-effect and lowest-effect levels for T-2-induced suppression of reovirus clearance were 20 and 200 microg/kg bw, respectively. Respiratory reovirus infection resulted in a mild bronchiolitis with minimal alveolitis, which was markedly exacerbated by T-2 pretreatment. Reovirus exposure induced marked increases in total cells, neutrophils and lymphocytes at 3 and 7 days PI in bronchial alveolar lavage fluid (BALF) whereas macrophages were increased only at 7 days PI. Although prior T-2 exposure attenuated total cell and macrophage counts in BALF of control and infected mice at 3 days PI, the toxin potentiated total cell, macrophage, neutrophil and lymphocyte counts in infected mice at 7 days PI. At 3 days PI, T-2 suppressed reovirus-induced IFN-gamma elevation in BALF, but enhanced production of IL-6 and MCP-1. T-2 pretreatment also suppressed reovirus-specific mucosal IgA responses in lung and enteric tract, but potentiated serum IgA and IgG responses. Taken together, T-2 increased lung viral burden, bronchopneumonia and pulmonary cellular infiltration in reovirus-infected mice. These effects might be attributable to reduced alveolar macrophage levels as well as modulated cytokine and mucosal Ig responses.
AuthorsMaoxiang Li, Jack R Harkema, Zahidul Islam, Chistopher F Cuff, James J Pestka
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 217 Issue 1 Pg. 76-85 (Nov 15 2006) ISSN: 0041-008X [Print] United States
PMID17005225 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • T-2 Toxin
Topics
  • Animals
  • Bronchiolitis, Viral (immunology, pathology)
  • Bronchoalveolar Lavage Fluid (immunology, virology)
  • Chemokine CCL2 (analysis)
  • Chemotaxis, Leukocyte (drug effects)
  • Cytokines (analysis, biosynthesis)
  • Dose-Response Relationship, Drug
  • Female
  • Immunoglobulin A (blood)
  • Immunoglobulin G (blood)
  • Immunosuppressive Agents (toxicity)
  • Interferon-gamma (analysis)
  • Interleukin-10 (analysis)
  • Interleukin-6 (analysis)
  • Lung (drug effects, immunology, pathology, virology)
  • Lymphocytes (drug effects, immunology, virology)
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils (drug effects, immunology, virology)
  • Orthoreovirus, Mammalian (immunology)
  • Reoviridae Infections (immunology, pathology)
  • Respiratory Mucosa (drug effects, immunology, virology)
  • T-2 Toxin (toxicity)
  • Tumor Necrosis Factor-alpha (analysis)
  • Viral Load

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