Research Article: Association of modifiable risk factors and IL-6, CRP, and adiponectin: Findings from the 1993 Birth Cohort, Southern Brazil

Date Published: May 9, 2019

Publisher: Public Library of Science

Author(s): Ana Maria Baptista Menezes, Paula Duarte Oliveira, Fernando César Wehrmeister, Maria Cecilia F. Assunção, Isabel O. Oliveira, Luciana Tovo-Rodrigues, Gustavo Dias Ferreira, Helen Gonçalves, Neha John-Henderson.

http://doi.org/10.1371/journal.pone.0216202

Abstract

The literature on the relationship between lifestyle behaviors and inflammatory markers is scarce.

A birth cohort was followed since birth up to 22 years in Southern Brazil. Interleukin-6 (IL-6), C-reactive protein (CRP) and adiponectin were measured in nonfasting blood samples drawn at 18 and 22 years of age. Exposures including smoking, alcohol intake, physical inactivity and obesity, were collected at 15, 18 and 22 years. Cross sectional analyses were based on the number of follow-up visits with these exposures and the association with IL-6, CRP and adiponectin at 22 years old. We also carried out a longitudinal Generalized Least Squares (GLS) random-effects analysis with outcomes at 18 and at 22 years old. All analyses were adjusted for several covariates.

The sample comprised 3,479 cohort members at 22 years. The presence of obesity at ≥ 2 follow-ups showed the highest mean values (SE) for IL-6 [2.45 (1.05)] and CRP [3.74 (1.11)] and the lowest mean value for adiponectin [8.60 (0.37)] (adjusted analyses, females) compared with other exposures; the highest mean of IL-6 [1.65 (1.05)] and CRP [1.78 (1.11)] and the lowest mean of adiponectin [9.98 (0.38)] were for the number of follow-ups with ≥2 exposures compared to those with no exposures at any follow-up (adjusted analyses, females). The longitudinal analysis showed an increase in obesity associated with IL-6 and CRP in both sexes and an inverse association with adiponectin in females; smoking (in males) was associated with IL-6 and CRP, harmful alcohol intake was associated with CRP in males, and increased in physical activity was inversely associated with CRP in men.

We concluded that obesity is the main exposure positively associated with IL-6 and CRP and inversely associated with adiponectin (mainly in females). Smoking is also associated with these markers in the longitudinal analysis (in males).

Partial Text

Increased levels of inflammatory markers, such as interleukin-(IL)-6 and C-reactive protein (CRP), predict the onset of poor health outcomes, particularly cardiovascular diseases and mortality [1, 2]. While the mechanisms that lead to increased values of these inflammatory markers are not completely understood, some risk factors, such as smoking, obesity and others, may be involved in the regulation of pro-inflammatory cytokines [3]; although circulating levels of IL-6 and CRP are physiologically linked, it remains unclear whether these markers track with one another with respect to several risk factors in healthy subjects. IL-6 stimulates the synthesis of CRP in the liver, and both markers are among the most commonly used indicators of inflammation.

All hospital births that occurred in the calendar year of 1993 in the city of Pelotas, Southern Brazil were assessed by daily visits to all maternity hospital [8]. Of the 5,265 live births in the city, 5,249 were enrolled in our birth cohort study. Subsamples of the cohort were followed up during childhood [9], and all cohort members were sought when they had reached the mean age of 11, 15, 18 and 22 years. All cohort time-lines and methodologies can be found in previous publications [8, 10]. For this study, all the participants who agreed to donate blood samples at 22 years of follow-up were included. Nonfasting blood samples were drawn by venipuncture using vacutainer tubes at the 18- and 22-year-old follow-up visit; samples were processed in the laboratory, stored at ultralow temperature freezers in the same place and registered in a central biorepository. IL-6 was measured by the Quantikine HS Human IL-6 immunoassay kit (R&D Systems, Inc.; Minneapolis, MN55413, USA), C-Reactive Protein (CRP) was measured by immunoturdimetric assay (Labtest Diagnóstica SA, Minas Gerais, Brazil) and adiponectin was assayed with the ELISA Quantikine Human Total Adiponectin Immunoassay kit (R&D Systems, Inc., Minneapolis, USA). At 18 years, adiponectin was measured in a random subsample (n = 275) due to financial limitations. Intra-assay and interassay coefficients of variation were, respectively, 4.10% and 13.6% for IL-6 and 9.1% and 13.2% for adiponectin. The interassay coefficient for CRP was 2.0%. The exclusion criteria for the blood samples were refusal to collect blood and pregnancy.

The 22 year follow-up comprised 3,810 cohort participants who were located and agreed to be interviewed (Fig 1). However, we have missing information for some variables and not all participants donated blood (N = 331), comprising a total of 3,479 cohort members for the present analysis. From this total, 52.3% were females (Table 1), most of the subjects reported white skin color, 41.2% had 9–11 years of schooling and 22.6% of the men belonged to the richest asset index quintile compared to 17% of the women. A greater proportion of women had common mental disorders (SRQ-20) than men (23.6% versus 19.6%), and a medical diagnosis of asthma was slightly more prevalent among males (Table 1). In males, the total prevalence of smoking varied from 2.3% at 15 years to 20.7% at 22 years, being higher among males than females, except at age 15 years.

This study demonstrates a direct association between the number of follow-up visits exposed to risk factors, such as smoking, alcohol consumption, inactivity and obesity as well the number of the number of risk factors, and the levels of IL-6 and CRP and an inverse association with adiponectin in a young adult Birth Cohort in Southern Brazil.

The association of inflammatory and anti-inflammatory markers with lifestyle modifiable risk factors and the additive effect of these risk factors in a healthy young population, analyzed in the present paper, can be of value in the prevention of chronic diseases.

 

Source:

http://doi.org/10.1371/journal.pone.0216202

 

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