Sex and strain-based inflammatory response to repeated tobacco smoke exposure in spontaneously hypertensive and Wistar Kyoto rats.
Approximately four million people die every year from chronic obstructive pulmonary disease (COPD), with more than 80% of the cases attributed to smoking.



The purpose of this study was to examine the rat strain and sex-related differences and the extended tobacco smoke exposure to induce lung injury and inflammation with the goal of finding a suitable rodent model to study COPD.



Male and female spontaneously hypertensive (SH) and male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or to tobacco smoke (TS: 90 mg/m3particulate concentration) for 6 h/day, three days/week for 4 or 12 weeks.



Male SH rats demonstrated an enhanced, persistent inflammatory response compared to female SH and male WKY rats with extended TS exposure. Following four weeks of TS exposure, male SH rats had significantly increased total leukocytes and macrophage numbers, levels of TNF-alpha and elevated lactate dehydrogenase activity in bronchoalveolar lavage fluid compared with female SH, male WKY rats and corresponding controls. After 12 weeks of TS exposure, male SH rats continued to show significant increase in inflammatory cells and TNF-alpha, as well as IL-6 mRNA lung expression. In addition, the alveolar airspace of male SH rats exposed to TS was significantly enlarged compared to their FA controls, female SH and WKY rats.



The male SH rat demonstrates greater cellular, inflammatory and structural changes highly reminiscent of COPD compared to female SH and male WKY rats, suggesting that the male SH rat is an optimal rodent model to study COPD.
a Center for Health and the Environment, University of California , Davis , CA , USA.
Yi-Hsin
YH
Shen
a Center for Health and the Environment, University of California , Davis , CA , USA.
Alexa K
AK
Pham
a Center for Health and the Environment, University of California , Davis , CA , USA.
Benjamin
B
Davis
a Center for Health and the Environment, University of California , Davis , CA , USA.
Suzette
S
Smiley-Jewell
a Center for Health and the Environment, University of California , Davis , CA , USA.
Lei
L
Wang
b Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park , NC , USA.
Urmila P
UP
Kodavanti
c Department of Animal Science , Kyoto Sangyo University , Kyoto , Japan , and.
Minoru
M
Takeuchi
d Department of Pediatrics and Center for Healthcare Policy and Research , University of California , Davis , CA , USA.
Daniel J
DJ
Tancredi
a Center for Health and the Environment, University of California , Davis , CA , USA.
Kent E
KE
Pinkerton
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012737:Sex Factors; D012906:Smoke / Q000009:adverse effects*; D013045:Species Specificity; D014026:Nicotiana
D016207:Cytokines; D012333:RNA, Messenger; D012906:Smoke; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
Lung inflammation; neutrophils; spontaneously hypertensive rats; tobacco smoke