A randomized cross-over study of inhalation of diesel exhaust, hematological indices, and endothelial markers in humans

Ranjini M. Krishnan, Jeffrey H. Sullivan, Chris Carlsten, Hui Wen Wilkerson, Richard P. Beyer, Theo Bammler, Fred Farin, Alon Peretz, Joel D. Kaufman

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Exposure to traffic-related air pollution (TRAP) is considered a trigger for acute cardiovascular events. Diesel Exhaust (DE) is a major contributor to TRAP in the world. We evaluated the effect of DE inhalation on circulating blood cell populations, hematological indices, and systemic inflammatory cytokines in humans using a specialized facility.Methods: In a randomized double-blind crossover study balanced to order, 17 metabolic syndrome (MetS) and 15 healthy subjects inhaled filtered air (FA) or DE exposure in two-hour sessions on different days with a minimum 2-week washout period. We collected blood pre-exposure, 7, and 22 hours after exposure initiation and measured the complete blood count and differential. We performed multiplex cytokine assay to measure the changes in the systemic inflammatory cytokines, and endothelial adhesion molecules (n=15). A paired analysis compared the effect of DE and FA exposures for the change from pre-exposure to the subsequent time points.Results: A significant increase in the hematocrit was noted 7 hrs after DE [1.4% (95% CI: 0.9 to 1.9%)] compared to FA exposure [0.5% (95% CI: -0.09 to 1.0%); p=0.008. The hemoglobin levels increased non-significantly at 7 hrs post DE [0.3 gm/dL (95% CI: 0.2 to 0.5 gm/dL)] versus FA exposure [0.2 gm/dL (95% CI: 0 to 0.3 gm/dL)]; p=0.06. Furthermore, the platelet count increased 22 hrs after DE exposure in healthy, but not in MetS subjects [DE: 16.6 (95% CI: 10.2 to 23) thousand platelets/mL versus [FA: 3.4 (95% CI: -9.5 to 16.3) thousand platelets/mL)]; p=0.04. No DE effect was observed for WBC, neutrophils, lymphocytes or erythrocytes. Using the multiplex assay, small borderline significant increases in matrix metalloproteinase-9, interleukins (IL)-1beta, 6 and 10 occurred 7 hrs post exposure initiation, whereas E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule -1, and myeloperoxidase 22 hrs post exposure.Conclusions: Our results suggest that short-term DE exposure results in hemoconcentration and thrombocytosis, which are important determinants of acute cardiovascular events. Multiplex assay showed a non-significant increase in IL-1β and IL-6 immediately post exposure followed by myeloperoxidase and endothelial activation molecules. Further specific assays in a larger population will improve our understanding of the systemic inflammatory mechanisms following acute exposure to TRAP.Clinical trials registration number: Study was conducted between 2004 to 2006, prior to expectation for registration.

Original languageEnglish
Article number7
JournalParticle and Fibre Toxicology
Volume10
Issue number1
DOIs
StatePublished - 28 Apr 2013
Externally publishedYes

Bibliographical note

Funding Information:
We would like to express our sincere appreciation to Mary Aulet, who coordinated the study and helped with the recruitment of the subjects and Jim Stewart for operating the controlled exposure facility. This study was funded by EPA grant RD-830954, NIEHS grants K24ES013195, K23ES1113901, P30ES07033, and P50 ES015915.

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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