Oral exposure of deltamethrin and/or lipopolysaccharide (LPS) induced activation of the pulmonary immune system in Swiss albino mice

Abstract

The deltamethrin, a synthetic pyrethroid, is used worldwide and has been linked with several type of acute toxicity. However, effect of low level of deltamethrin alone or in combination with the microbial antigen on pulmonary system is not understood. Lipopolysaccharide (LPS) was used as antigen which is a key inflammatory component of gram-negative bacteria, which induces a distinctive pattern of cytokine release that regulates inflammation. The aim was to determine whether chronic exposure to a low level of deltamethrin alone or in combination with LPS impair the lung response in adult male Swiss albino mice. The mice were orally exposed to different doses of deltamethrin (0.1, 0.05, 0.005, 0.001 mg/kg bwt) and then immunized with LPS at the 60th day. None of the treatment groups contained residues of deltamethrin above the limits of quantification. Deltamethrin combined with LPS challenge caused significant lymphocytosis and neutropenia in group 1 (0.1 mg/kg) mice (P < 0.05). The highest dose of deltamethrin exposure (0.1 mg/kg bwt) alone altered the total cell count significantly in blood and total leukocyte count (TLC) and macrophage count in bronchoalveolar lavage fluid. Microscopic pulmonary damage was evaluated by H&E staining and EM which indicated that two higher doses of deltamethrin, i.e., 0.1 and 0.05 mg/kg bwt, distinctly increased inflammatory cell infiltration and caused alveolar septa thickening and leukocyte infiltration into the alveolar septum (septal cell infiltration) in the lungs. Deltamethrin exposure alone and/or with endotoxin revealed different degrees of immunopositive reaction for Toll-like receptor 4 (TLR4) and pro-inflammatory cytokine-like tumor necrosis factor-alpha (TNFα) in different parts of the lungs. The expression of TLR4 and TNFα in the lung tissue was more pronounced in two higher dose groups. Thus, chronic low-level deltamethrin exposure may impair the main pro-inflammatory response in the lungs which is more pronounced in combination with LPS. Further research is required in direction of the mechanism of action of deltamethrin on the immune cell lineage and their differentiation.