Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate.
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-1beta (IL1beta), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (INTgamma), 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 IL1beta, TNFalpha 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 IgMhi IgDhi, IgMlo IgDlo and CD8+ CD45RA- CCR7+ cells were elevated, while IgMlo IgDhi, IgMhi IgDlo, IgMin IgDlo, 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.
Singh
A K
AK
Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St Paul Campus, St Paul, MN, USA. singh001@tc.umn.edu
Jiang
Y
Y
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D016207:Cytokines; D004347:Drug Interactions; D007136:Immunoglobulins / Q000032:analysis; D007249:Inflammation; D007306:Insecticides / Q000633:toxicity*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010641:Phenotype; D063088:Phosphoramides; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D007136:Immunoglobulins; D007306:Insecticides; D008070:Lipopolysaccharides; D009946:Organothiophosphorus Compounds; D063088:Phosphoramides; C001969:acephate