MISSION

and signaling functions), is suppressed by CS. In the Beas-2b transformed airway epithelial cell line, CS
exposure decreased the antimicrobial activity of these cells and decreased transcription and secretion of the
protein CCL20. The investigators also measured CCL20 in nasal washes of human subjects and found that
those exposed to CS or SHS had decreased concentrations of CCL20 compared to non-smokers. Even
subjects with prior, but not recent, CS exposure had low CCL20 levels implying that the immune response
of epithelial progenitor cells is impaired in a permanent manner by CS exposure. Dr. Jukosky seeks to verify
his preliminary data and test the production of other related antimicrobial and signaling molecules in
humans with no CS exposure, prior CS exposure (6 months to 5 years ago), current SHS exposure, and
subjects with current primary CS exposure (smokers). In Aim 1 the investigators are testing the hypothesis
that CS alters both constitutive production and induction by lipotechoic acid (LTA) challenge of important
innate immune molecules from primary human nasal epithelial (PHNE) cells. In Aim 2, the study
focuses on the nasal secretions of the same volunteers and test the hypothesis that cigarette smoke exposure
alters the steady-state levels of the same innate immune molecules in the nasal passage. Taken together,
these studies will provide in vivo evidence of the effects of CS exposure on the immune function of
PHNE and show whether prior CS exposure induces permanent changes in the progenitor cells in the
nasal mucosa. The results of these studies should improve understanding of how CS exposure influences
the development of infection in the upper airways, thus aiding in future prevention, diagnosis and treatment,
as well as educational efforts for public awareness about the dangers of CS exposure.
IMMUNE FUNCTION IMPACTED BY TOBACCO SMOKE
COMPLETED RESEARCH
ONTOGENY OF CYTOKINE IMMUNE RESPONSES: ROLE OF SECOND HAND TOBACCO SMOKE
Deborah A. Gentile, MD; Allegheny-Singer Research Institute; CIA 2004
SHS is a risk factor for the development of childhood asthma. Dr. Gentile compared subjects with and
without exposure to SHS (determined by serum cotinine levels). The number of dendritic cells and
CD4+CD25+ cells in those individuals without exposure was significantly higher than in those who had
been exposed to SHS. No significant differences were seen in CD8+CD38+ lymphocytes or cyokine
production in these two groups, but there were age-related decreases in the absolute numbers of
CD4+CD25+ cells, CD8+CD38+ lymphocytes, and dendritic cells. CD8+ cells that produce interleukin
(IL) 4 and IL13 also decreased in number with respect to age. However, interferon (IFN) gamma from
CD8+ cells and cytokines from CD4+ cells and dendritic cells did not decrease as a function of age. These
results indicate that there is a differential immune response in children related to age and related to
exposure to SHS.
INFECTIOUS DISEASES
CURRENT RESEARCH
SHS AND INFLUENZA-INDUCED RESPONSES IN NASAL EPTHELIUM
Ilona Jaspers, PhD; University of North Carolina at Chapel Hill; CIA 2006
Exposure to SHS has been associated with increased susceptibility to infection with respiratory viruses.
Influenza virus infections continue to cause significant mortality and morbidity in the United States and
worldwide every year. However, there are few data on the effects of SHS exposures on influenza infections
in humans. The objectives of this project are to determine whether exposure to SHS enhances the
susceptibility to influenza virus infections in humans in vivo and whether this effect is mediated by SHSinduced
oxidative stress. The proposed study is subdivided into two interdependent studies: One which
will determine the effects of SHS exposure on influenza infections in healthy human volunteers in vivo,
and one which uses an in vitro model of differentiated human nasal epithelial cells to confirm and expand
the in vivo findings, and to examine potential cellular mechanisms mediating the effects of SHS on
influenza virus infections. For the human in vivo study, Dr. Jasper is measuring the effects of naturally
occurring SHS exposure on influenza infections in human volunteers in vivo using the live attenuated
influenza virus (LAIV) vaccine. This vaccine is a cold-adapted influenza virus that infects and replicates in
the nasal epithelium, without spreading to the lower airways and inducing serious adverse health effects. A
small group of smokers were also recruited for comparison. Preliminary analyses indicate that markers of
viral replication are increased in individuals exposed to SHS compaired to non-exposed controls. Study
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