Side-stream cigarette smoke induces dose-response in systemic inflammatory cytokine production and oxidative stress

Jin Zhang, Yingying Liu, Jiaqi Shi, Douglas F. Larson, Ronald Ross Watson

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Side-stream cigarette smoke (SSCS), a major component of secondhand smoke, induces reactive oxygen species, which promote oxidative damage in tissues and organs. Inflammatory cytokines play an important role in the pathogenesis of atherosclerosis and heart failure. The present 4-month study examined the effect of various chronic SSCS exposure levels on splenic inflammatory cytokine secretion, heart contractile function, and pathology at 60- and 120-min per day, 5 days per week, for a total of 16 weeks. Tissue vitamin E level and lipid peroxide production also were tested to estimate the oxidative stress. The study found that the pro-inflammatory cytokines, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β0, significantly increased in 120-min SSCS-exposed mice. Decreased stroke volume and increased peripheral arterial resistance were observed in mice exposed to 120-min SSCS per day. Heart pathology was only found in 120-min SSCS-exposed mice. Cardiac and hepatic antioxidant vitamin E levels were decreased as a result of oxidative stress. Hepatic lipid peroxides were increased upon 60-min SSCS exposure. The data also demonstrated that the cardiac α-tocopherol level has a strong correlation with stroke volume; splenic IL-1β has a strong negative correlation with stroke volume; splenic TNF-α has a very strong negative correlation with stroke volume. In conclusion, SSCS exposure induced systemic inflammatory responses. SSCS exposure also accentuated systemic lipid peroxidation with depletion of cardiac and hepatic antioxidant vitamin E level. Finally, SSCS exposure at 120 min per day decreased stroke volume and increased vascular resistance. Systemic IL-1β and TNF-α production are responsible for heart contractile dysfunction. Free radicals may be responsible for the progression to heart contractile dysfunction induced, in part, by SSCS. Oxidized lipoprotein could contribute to the vascular functional changes. Exploring the mechanism of vascular dysfunction in mice is warranted. A more precise quantification of the smoking exposure dose in mice needs to be determined as well.

Original languageEnglish (US)
Pages (from-to)823-829
Number of pages7
JournalExperimental Biology and Medicine
Issue number9
StatePublished - Oct 2002


  • Arterial resistance
  • Cardiac vitamin E
  • Pro-inflammatory cytokines

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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