Chlorpyriphos induces lung inflammation and alters response to E. coli lipopolysaccharide challenge

Abstract

Pesticided chlorpyriphos (CP), recently found in fodder and food in Punjab (India), has been linked to respiratory dysfunction. Because the effects of CP on lung immunity are not fully known, we studied that by exposing the mice to CP (3mg/kg/d orally for 60 d; N=20) followed by intranasal E. coli LPS (80μg) or normal saline (n=10 each). The mice were euthanized 12 hours post‐LPS treatment. Control mice (n=10 each) were given saline or the LPS alone. Mice treated both with CP and LPS had increase in total cell counts and leukocyte counts in broncho‐alveolar lavage (BAL) compared to other groups groups (P<0.05). Control mice showed normal lung histology compared to peribronchial and perivascular cell infiltration, loss of cilia, and congestion in 60d CP mice. While LPS induced acute inflammation in the lungs, combination of CP and LPS exacerbated histological signs of the inflammation. CP challenge increased lung staining of TNFα compared to control mice but not LPS or CP+LPS mice. TLR4, which ligates LPS, expression was increased in the airway epithelium, macrophages and alveolar septa of mice treated with CP or the LPS compared to the control. There were increased numbers of TLR9‐positive cells in lungs of CP‐treated mice compared to the control and the LPS groups but not CP+LPS mice (P<0.05). The data show CP caused lung inflammation and altered TLR expression which may have led to altered response to LPS challenge. Funding: GADVASU and UofSask