The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants.
This study was designed to examine the role of the cytokine interleukin-6 (IL-6) in environmental air pollutant-induced pulmonary inflammation, injury, and repair. IL-6 knockout (KO) mice and wild-type (WT) mice were exposed to filtered air; aged and diluted cigarette smoke (ADSS), a surrogate for environmental tobacco smoke; ozone; or ADSS followed by ozone (ADSS/ozone). The proportion of monocytes and neutrophils recovered by bronchoalveolar lavage (BAL) as well as the level of total protein in BAL fluid were significantly increased in both IL-6 KO and WT mice following exposure to ozone or to ADSS/ozone. However, bromodeoxyuridine (BrdU) labeling within terminal bronchiolar epithelium and proximal alveolar regions in IL-6 KO mice exposed to ozone or to ADSS/ozone was significantly reduced compared with IL-6 sufficient mice (WT). WT mice treated with IL-6 antibodies also demonstrated a reduction in BrdU cell labeling similar to that observed in IL-6 KO mice following exposure to ozone or ADSS/ozone. Clara cell secretory protein (CCSP) abundance, a marker of Clara cell maturation and function, was markedly reduced in the terminal bronchiolar epithelium of WT mice following exposure to ADSS and/or ozone, whereas CCSP abundance was unchanged in IL-6 KO mice. We conclude that endogenous IL-6 in mice plays a critical role in the progress of lung inflammation/injury, but CCSP may also play a role to protect the lungs of mice exposed to toxic air pollutants. Data from this study further suggest that IL-6 antibody treatment modalities may be a means to attenuate pulmonary inflammation and injury.
Yu
Mang
M
Center for Comparative Respiratory Biology and Medicine, University of California, Davis, California 95616, USA.
Zheng
Xiaomu
X
Witschi
Hanspeter
H
Pinkerton
Kent E
KE
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004338:Drug Combinations; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014598:Uteroglobin
D000393:Air Pollutants; D004338:Drug Combinations; D015850:Interleukin-6; C556390:Scgb1a1 protein, mouse; D014028:Tobacco Smoke Pollution; D010126:Ozone; D014598:Uteroglobin; D001973:Bromodeoxyuridine