Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate

Ashok K Singh, Yin Jiang

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22 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1b (IL1b), tumor necrosis factor-a (TNFa), interferon-g (INTg), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1b, TNFa and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhiIgDhi, IgMloIgDloand CD8+CD45RA CCR7+cells were elevated, while IgMloIgDhi, IgMhiIgDlo, IgMinIgDlo, CD8+CD45RA +CCR7+and CD8+CD45RACCR7+cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.

Original languageEnglish (US)
Pages (from-to)93-108
Number of pages16
JournalToxicology and Industrial Health
Volume19
Issue number6
DOIs
StatePublished - Jan 1 2003

Fingerprint

acephate
Organothiophosphates
Rat control
Immune system
Insecticides
Lipopolysaccharides
Rats
Immune System
Chemical activation
Cytokines
Lymphocytes
Blood
Anti-Inflammatory Agents
Interleukins
Corticotropin-Releasing Hormone
Nitric Oxide Synthase Type II
Corticosterone
Interleukin-4
Brain
Tumor Necrosis Factor-alpha

Keywords

  • B and T cells
  • TNFα
  • acephate
  • interferon γ
  • interleukin 1β
  • interleukin 4
  • lipopolysaccharide (LPS)
  • lymphocytes

Cite this

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title = "Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate",
abstract = "Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1b (IL1b), tumor necrosis factor-a (TNFa), interferon-g (INTg), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1b, TNFa and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhiIgDhi, IgMloIgDloand CD8+CD45RA −CCR7+cells were elevated, while IgMloIgDhi, IgMhiIgDlo, IgMinIgDlo, CD8+CD45RA +CCR7+and CD8+CD45RA−CCR7+cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.",
keywords = "B and T cells, TNFα, acephate, interferon γ, interleukin 1β, interleukin 4, lipopolysaccharide (LPS), lymphocytes",
author = "Singh, {Ashok K} and Yin Jiang",
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T1 - Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate

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N2 - Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1b (IL1b), tumor necrosis factor-a (TNFa), interferon-g (INTg), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1b, TNFa and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhiIgDhi, IgMloIgDloand CD8+CD45RA −CCR7+cells were elevated, while IgMloIgDhi, IgMhiIgDlo, IgMinIgDlo, CD8+CD45RA +CCR7+and CD8+CD45RA−CCR7+cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.

AB - Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1b (IL1b), tumor necrosis factor-a (TNFa), interferon-g (INTg), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1b, TNFa and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhiIgDhi, IgMloIgDloand CD8+CD45RA −CCR7+cells were elevated, while IgMloIgDhi, IgMhiIgDlo, IgMinIgDlo, CD8+CD45RA +CCR7+and CD8+CD45RA−CCR7+cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.

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KW - interferon γ

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KW - interleukin 4

KW - lipopolysaccharide (LPS)

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