Factors associated with inflammation markers, a cross-sectional analysis
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].
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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.
References (74)
Vitamin D and the immune system: new perspectives on an old theme
Endocrin Metab Clin
(2010)Reproducibility of serum cytokines and growth factors
Cytokine
(2009)Multiplexed particle-based flow cytometric assays
J Immunol Meth
(2000)Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal
Fertil Steril
(2002)Postmenopausal changes in serum cytokine levels and hormone replacement therapy
Am J Obstet Gynecol
(2001)Changes in serum cytokine concentrations during the menopausal transition
Maturitas
(2007)Cytokine pattern in postmenopause
Maturitas
(2002)Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay
J Am Coll Cardiol
(2001)Effects of aspirin (325 mg/day) on serum high-sensitivity C-reactive protein, cytokines, and adhesion molecules in healthy volunteers
Am J Cardiol
(2003)Relation of smoking status to a panel of inflammatory markers: the framingham offspring
Atherosclerosis
(2008)