Elsevier

Cytokine

Volume 56, Issue 3, December 2011, Pages 769-778
Cytokine

Factors associated with inflammation markers, a cross-sectional analysis

https://doi.org/10.1016/j.cyto.2011.09.013Get rights and content

Abstract

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.

Highlights

► We assessed potential determinants of inflammation markers among 616 healthy women. ► Observed associations between lifestyle and reproductive factors and inflammation markers. ► Associations: age, BMI, menopause, parity, NSAIDs, family history of cancer, smoking.

Introduction

Several studies have shown that elevated inflammation markers, primarily C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNFα), are associated with increased risk of cardiovascular disease, type II diabetes, and other chronic conditions, including cancer [1], [2], [3], [4], [5], [6], [7], [8], [9]. We recently conducted a case–control study of ovarian cancer nested in three prospective cohorts, and found that IL-2, IL-4, IL-6, IL-12, and IL-13 were associated with risk [10]. Several inflammation-related markers, including IL-2, IL-5, TNFβ, interferon γ (IFNγ), ICAM, soluble IL-2 receptor (sIL-2R), and soluble TNFα receptor 1 (sTNF-R1), have been found to be positively, and IL-13 inversely, associated with subsequent risk of non-Hodgkin lymphoma (NHL) [11], [12], [13]. Given the potential role of inflammation in chronic disease, it is of interest to identify factors that contribute to differences in levels of inflammation markers among healthy people.

The emphasis of previous studies has generally been on the association between a limited number of inflammation markers (usually CRP, IL-6, and TNFα) and general lifestyle and/or cardiovascular risk factors [1], [14], [15]. The focus of the present study was to assess whether reproductive and lifestyle factors and circulating vitamin D, which is immunomodulatory and has anti-inflammatory properties in vitro [16], [17], are associated with CRP, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNFα) and cytokine modulators/soluble receptors (IL-1 receptor antagonist (Ra), soluble (s)IL-1RII, sIL-2Ra, sIL-4R, sIL-6R, and sTNF-R1/R2) in healthy women. We selected inflammation markers that showed adequate temporal reproducibility (ICC  0.5) over a 2–3 year period in preliminary reproducibility studies, thus suggesting that a single inflammation marker measurement can be used to rank women according to their average level [18], [19], [20].

Section snippets

Study subjects

For these cross-sectional analyses, we included healthy controls from two nested case–control studies in which inflammation markers have been measured: (1) a study of ovarian cancer in three prospective cohorts: the New York University Women’s Health Study (NYUWHS-OVCA), the Northern Sweden Health and Disease Study (NSHDS), and ORDET in Italy [10]; and (2) a study of non-Hodgkin lymphoma in the NYUWHS cohort (NYUWHS-NHL) [11]. The parent cohorts have been described in detail previously [21],

Results

Characteristics of the study subjects are shown in Table 1. The age range at blood sampling was 30–75 years (mean = 55 years), and 66% of the women were post-menopausal. The median BMI was about 25 kg/m2. Thirty-five percent of women had previously used oral contraceptives, 23% were nulliparous, and 82% of parous women had 2 or more children. 18% of women reported having a first-degree family history of breast or ovarian cancer. At the time of blood sampling, 18% were current smokers, 17% were

Discussion

Our results support three previous studies that observed higher levels of the pro-inflammatory cytokine TNFα among post-menopausal women [31], [32], [33], although others did not observe such a difference [34], [35], or observed lower levels [36]. Two soluble cytokine receptors, sIL-1RII and sIL-2Ra were also higher among post- vs. pre-menopausal women. The associations were apparent after adjustment for age and BMI, which suggests that these markers may be influenced by sex hormones.

Increasing

Acknowledgements

This work was supported by research grants from the National Cancer Institute (R21 CA116585, R01 CA098661, and P30CA016087) and the National Institute of Environmental Health Sciences Center Grant (ES000260) at the National Institutes of Health.

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