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Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype
  1. Madeline A Dillon1,
  2. Bradford Harris1,
  3. Michelle L Hernandez1,
  4. Baiming Zou1,
  5. William Reed1,
  6. Philip A Bromberg1,
  7. Robert B Devlin2,
  8. David Diaz-Sanchez2,
  9. Steven Kleeberger3,
  10. Haibo Zhou1,
  11. John C Lay1,
  12. Neil E Alexis1,
  13. David B Peden1
  1. 1Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  2. 2Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina, USA
  3. 3Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
  1. Correspondence to David B Peden, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7310, USA; peden{at}med.unc.edu

Abstract

Objective To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin.

Methods 35 volunteers who had undergone inhalation challenge with a 20 000 endotoxin unit dose of Clinical Center Reference Endotoxin (CCRE) were genotyped for the GSTM1 null polymorphism. Parameters of airway and systemic inflammation observed before and after challenge were compared in GSTM1 null (n=17) and GSTM1 (n=18) sufficient volunteers.

Results GSTM1 null volunteers had significantly increased circulating white blood cells (WBCs), polymorphonuclear neutrophils (PMNs), platelets and sputum PMNs (% sputum PMNs and PMNs/mg sputum) after CCRE challenge. GSTM1 sufficient volunteers had significant, but lower increases in circulating WBCs, PMNs and % sputum PMNs, and no increase in platelets or PMNs/mg sputum. Linear regression analysis adjusted for baseline values of the entire cohort revealed that the GSTM1 null genotype significantly increased circulating WBCs, platelets and % sputum PMNs after challenge.

Conclusion These data support the hypothesis that the GSTM1 null genotype is a risk factor for increased acute respiratory and systemic inflammatory response to inhaled CCRE. These data are consistent with other observations that the GSTM1 null genotype is associated with increased respiratory, systemic and cardiovascular effects linked to ambient air particulate matter exposure and indicate that the GSTM1 null genotype should be considered a risk factor for adverse health effects associated with exposure to environmental endotoxin.

  • Toxicology
  • bronchitis
  • respiratory
  • environment

https://doi.org/10.1136/oem.2010.061747

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    Footnotes

    • Funding This research was supported in part by grants R01ES012706, RC1ES018417 and P30010126 from the National Institute of Environmental Health Sciences, U19AI077437 from the National Institute for Allergy and Infectious Diseases, P01AT002620 from the National Center for Complementary and Alternative Medicine, and KL2RR025746, M01RR00046 and UL1RR025747 from the National Center of Research Resources of the National Institutes of Health, as well as CR 83346301 from the US Environmental Protection Agency. Although the research described herein has been funded in part by the United States Environmental Protection Agency, it has not been subjected to the EPA's required peer and policy review. The findings contained in this report do not necessarily reflect the views of the Environmental Protection Agency or the National Institutes of Health, and no official endorsement should be inferred.

    • Competing interests BH has received research support from the National Institute of Environmental Health Sciences, US Environmental Protection Agency and Purdue Pharmaceuticals-Quintiles. PAB has received support from the US Environmental Protection Agency and National Institute of Health. DBP has consulted for GlaxoSmithKline and Funxional Therapeutics and has received research support from the National Institute of Environmental Health Sciences, the National Center for Complementary and Alternative Medicine, the National Heart, Lung, and Blood Institute, the National Institute for Allergy and Infectious Diseases, the US Environmental Protection Agency and the National Center for Research Resources. The rest of the authors have declared that they have no competing interests.

    • Ethics approval This study was conducted with the approval of the IRB at the University of North Carolina.

    • Provenance and peer review Not commissioned; externally peer reviewed.