Proinflammatory and anti-inflammatory cytokine balance in gasoline exhaust induced pulmonary injury in mice.
Proinflammatory and anti-inflammatory cytokine balance and associated changes in pulmonary bronchoalveolar lavage fluid (BALF) of unleaded gasoline exhaust (GE) exposed mice were investigated. Animals were exposed to GE (1 L/min of GE mixed with 14 L/min of compressed air) using a flow-past, nose-only, dynamic inhalation exposure chamber for different durations (7, 14, and 21 days). The particulate content of the GE was found to be 0.635, +/-0.10 mg PM/m3. Elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were observed in BALF of GE-exposed mice, but interleukin 1beta(IL-1beta) and the anti-inflammatory cytokine interleukin-10 (IL-10) remained unaffected. GE induced higher activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (gammaGT), and lactate dehydrogenase (LDH) in the BALF, indicating Type II alveolar epithelial cell injury, Clara-cell injury, and general toxicity, respectively. Total protein in the BALF increased after 14 and 21 days of exposure, indicating enhanced alveolar-capillary permeability. However, the difference in the mean was found statistically insignificant in comparison to the compressed air control. Total cell count in the BALF of GE-exposed mice ranged between 0.898 and 0.813x10(6) cells/ml, whereas the compressed air control showed 0.65x10(6) cells/mL. The histopathological changes in GE-exposed lung includes perivascular, and peribronchiolar cuffing of mononuclear cells, migration of polymorphonuclear cells in the alveolar septa, alveolar thickening, and mild alveolar edematous changes indicating inflammation. The shift in pro- and anti-inflammatory cytokine balance and elevation of the pulmonary marker enzymes indicate toxic insult of GE. This study will help in our understanding of the mechanism of pulmonary injury by GE in the light of cytokine profiles, pulmonary marker enzymes, and lung architecture.
Sureshkumar
Veerapandian
V
Inhalation Toxicology Laboratory, Industrial Toxicology Research, Center Mahatma Gandhi Marg, Lucknow, India.
Paul
Bholanath
B
Uthirappan
Mani
M
Pandey
Renu
R
Sahu
Anand Prakash
AP
Lal
Kewal
K
Prasad
Arun Kumar
AK
Srivastava
Suresh
S
Saxena
Ashok
A
Mathur
Neeraj
N
Gupta
Yogendra Kumar
YK
D000280:Administration, Inhalation; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D005742:Gasoline / Q000633:toxicity*; D007249:Inflammation; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D001335:Vehicle Emissions / Q000633:toxicity*; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
D015415:Biomarkers; D016207:Cytokines; D005742:Gasoline; D001335:Vehicle Emissions; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase