Elsevier

Cytokine

Volume 60, Issue 1, October 2012, Pages 34-37
Cytokine

Short Communication
Secondhand smoke exposure and serum cytokine levels in healthy children

https://doi.org/10.1016/j.cyto.2012.06.236Get rights and content

Abstract

Introduction

Exposure to secondhand smoke (SHS) is associated with morbidity in children. Alterations in immune responses may explain this relationship, but have not been well-studied in children. Our objective was to determine the association between SHS exposure and serum cytokine levels in healthy children.

Methods

We recruited 1–6 year old patients undergoing routine procedures. A parent interview assessed medical history and SHS exposure. Children with asthma were excluded. Blood was collected under anesthesia. We used Luminex Multiplex Assays to test for a panel of cytokines; cotinine was determined using an enzyme-linked immunosorbent assay. Children were categorized as no, intermediate, or high exposure. A mixed-effects model was fit to determine differences in cytokines by exposure level.

Results

Of the 40 children recruited, 65% (N = 26) had SHS exposure; 16 intermediate, and 10 high. There were no differences by demographics. In bivariate analyses, children exposed to SHS had lower concentrations of IL-1β, IL-4, IL-5, and IFN-γ than those with no exposure. In the mixed-effects model, children with any SHS exposure had significantly lower concentrations of IL-1β (0.554 pg/mL vs. 0.249 pg/mL) and IFN-γ (4.193 pg/mL vs. 0.816 pg/mL), and children with high exposure had significantly lower mean concentrations of IL-4 (8.141 pg/mL vs. 0.135 pg/mL) than children with no exposure.

Conclusions

This study suggests that SHS exposure decreases expression of some pro-inflammatory cytokines in SHS exposed children, including IFN-γ. Further research to describe the acute and chronic effects of SHS on the immune systems of children is needed.

Highlights

► Circulating cytokines can be measured in children. ► Certain cytokines are lower in children exposed to secondhand tobacco smoke. ► Further research is needed to explore these links.

Introduction

Secondhand smoke (SHS) exposure is a significant source of morbidity within the pediatric population. A variety of diseases are associated with SHS exposure, including lower respiratory infections [1], asthma [2], and otitis media [3]. It is estimated that each year in the US, 202,300 new cases of asthma, 300,000 cases of lower respiratory illnesses, and 789,700 ear infections develop due to SHS exposure in children [4].

The relationship between SHS exposure and the development of these diseases is not yet fully understood. Evidence from both human and animal models suggests that SHS exposure may increase local and systemic inflammatory states, and has effects on a variety of types of cytokines, including both TH1 and TH2 (or atopic) responses. In one animal study, mice exposed to SHS had increased circulating levels of interleukin-1β (IL-1β), a pro-inflammatory cytokine [5]. In humans, exposure to SHS increases expression of inflammatory cytokines associated with the TH2 response, including IL-4, IL-5 and IL-6 [6]. Elevated serum levels of these cytokines have been described for up to 3 h after exposure [6].

Children exposed to SHS have elevated upper airway secretions of IL-13 [7]. The elevation of pro-inflammatory cytokines at both the systemic and local levels may account for the poor respiratory health of children exposed to SHS, and the predisposition of exposed children to develop asthma. In older children, SHS exposure has also been shown to decrease levels of interferon-γ (IFN-γ) as detected from mitogen stimulated mononuclear cells; INF-γ is involved in protection against viral and bacterial pathogens [8]. Suppression of immune responses may account for the increased prevalence and severity of illness in SHS-exposed children.

Despite the evidence that SHS exposure results in altered inflammatory states, the mechanism and scope of these changes are not fully understood, especially in children. Few studies have measured circulating cytokines in this population. In order to determine the association between SHS exposure and serum markers of inflammation in a pediatric population, we completed a pilot study of 40 healthy children undergoing routine operative procedures to determine (1) whether we could measure cytokine levels in the serum of healthy children, and (2) if there were differences between the cytokine levels of SHS exposed and non-exposed children.

Section snippets

Patients

This study took place at Golisano Children’s Hospital at the University of Rochester Medical Center in Rochester, NY from 2009–2010. Patients included healthy children ages 1–6 years, undergoing routine same-day operative procedures. Patients who had illness symptoms, such as cough or rhinorrhea, were excluded from the study, as were patients with active medical conditions, including asthma, allergies, and eczema, or if anti-inflammatory medications were taken in the 2 weeks preceding the study.

Results

A total of 40 children were included in the study. The mean age was 3.55 years (range 1–6 years); 50% were males, 87.5% white, 5% African-American, 5% Hispanic, and 2.5% multiracial. The operative procedures included 70% dental restorations, 17.5% endoscopies, and 12.5% otolarygologic procedures. Two (5%) children did indicate having a history of eczema; however it was not active at the time of the study and they were on no medications. Other medical conditions noted included autism, celiac

Discussion

Understanding the effect of tobacco smoke exposure on the expression of a broad variety of cytokines in children will help us better capture the complex interaction between tobacco smoke and the immune system, and develop interventions for children who continue to be exposed. Since few studies have examined serum expression of cytokines in children, and fewer have compared the levels between smoke-exposed and non-smoke-exposed children, it is important to recognize that a broad range of

Conclusions

Healthy children who are exposed to SHS have decreased IFN-γ expression compared to those who are not SHS-exposed. Pediatricians and other providers of care to children should understand the biochemical risks of exposure, and how this may affect children’s immune function, so that they may properly counsel parents about the benefits of smoking cessation and smoke exposure reduction. Further research to describe the acute and chronic effects of SHS on the immune systems of children is needed.

Authors’ Contributions

KW participated in the study conception, design, analysis, interpretation of results, and manuscript revision. SP and SW participated in the acquisition and preliminary analysis of the data, as well as drafting and revising the manuscript. EW participated in study conception and design, interpretation of results, as well as revision of the manuscript. TL and KE played a substantial role in data analysis and interpretation of the findings, as well as manuscript revision. AC was involved in the

Acknowledgements

This research was supported by the Strong Children’s Research Center and the Flight Attendant Medical Research Institute (FAMRI) through a grant from the AAP Julius B. Richmond Center of Excellence.

We would like to acknowledge Pediatric Anesthesia, the Pediatric Surgery Division, and Dr. Robert Berkowitz for their cooperation in subject recruitment. We would also like to acknowledge the Human Immunology Core Lab at the University of Rochester for laboratory analyses.

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