Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Behavioral Medicine
Published in: Annals of Behavioral Medicine 4/2016

Open Access 01-08-2016 | Original Article

Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men

Authors: Romano Endrighi, PhD, Mark Hamer, PhD, Andrew Steptoe, DPhil

Published in: Annals of Behavioral Medicine | Issue 4/2016

Login to get access

Abstract

Background

Acute stress triggers innate immune responses and elevation in circulating cytokines including interleukin-6 (IL-6). The effect of sex on IL-6 responses remains unclear due to important limitations of previous studies.

Purpose

The purpose of this study was to examine sex differences in IL-6 responses to mental stress in a healthy, older (post-menopausal) sample accounting for several moderating factors.

Methods

Five hundred six participants (62.9 ± 5.60 years, 55 % male) underwent 10 min of mental stress consisting of mirror tracing and Stroop task. Blood was sampled at baseline, after stress, and 45 and 75 min post-stress, and assayed using a high sensitivity kit. IL-6 reactivity was computed as the mean difference between baseline and 45 min and between baseline and 75 min post-stress. Main effects and interactions were examined using ANCOVA models.

Results

There was a main effect of time for the IL-6 response (F 3,1512 = 201.57, p = <.0001) and a sex by time interaction (F 3,1512 = 17.07, p = <.001). In multivariate adjusted analyses, IL-6 reactivity was significantly greater in females at 45 min (M = 0.37 ± 0.04 vs. 0.20 ± 0.03 pg/mL, p = .01) and at 75 min (M = 0.57 ± 0.05 vs. 0.31 ± 0.05 pg/mL, p = .004) post-stress compared to males. Results were independent of age, adiposity, socioeconomic position, depression, smoking and alcohol consumption, physical activity, statin use, testing time, task appraisals, hormone replacement, and baseline IL-6. Other significant predictors of IL-6 reactivity were lower household wealth, afternoon testing, and baseline IL-6.

Conclusions

Healthy, post-menopausal females exhibit substantially greater IL-6 responses to acute stress. Inflammatory responses if sustained over time may have clinical implications for the development and maintenance of inflammatory-related conditions prevalent in older women.
Literature
1.
Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychol Bull. 2014, 140:774–815.
2.
Steptoe A, Kivimaki M. Stress and cardiovascular disease. Nat Rev Cardiol. 201;9:360–370.
3.
Brydon L, Steptoe A. Stress-induced increases in interleukin-6 and fibrinogen predict ambulatory blood pressure at 3-year follow-up. J Hypertens. 2005;23:1001–1007.
4.
Bierhaus A, Wolf J, Andrassy M, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U.S.A. 2003;100:1920–1925.
5.
Brydon L, Edwards S, Jia H, et al. Psychological stress activates interleukin-1beta gene expression in human mononuclear cells. Brain Behav Immun. 2005;19:540–546.
6.
Kuebler U, Zuccarella-Hackl C, Arpagaus A, et al. Stress-induced modulation of NF-kappaB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men. Brain Behav Immun. 2015;46:87–95.
7.
Wolf JM, Rohleder N, Bierhaus A, Nawroth PP, Kirschbaum C. Determinants of the NF-kappaB response to acute psychosocial stress in humans. Brain Behav Immun. 2009;23:742–749.
8.
Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med. 2014;76:181–189.
9.
Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: A review and meta-analysis. Brain Behavior Immunity. 2007;21:901–912.
10.
McInnis CM, Thoma MV, Gianferante D, et al. Measures of adiposity predict interleukin-6 responses to repeated psychosocial stress. Brain Behav Immun. 2014;42:33–40.
11.
von KR, Kudielka BM, Preckel D, Hanebuth D, Fischer JE. Delayed response and lack of habituation in plasma interleukin-6 to acute mental stress in men. Brain Behav Immun. 2006;20:40–48.
12.
Ellins E, Halcox J, Donald A, et al. Arterial stiffness and inflammatory response to psychophysiological stress. Brain Behav Immun. 2008;22:941–948.
13.
Steptoe A, Owen N, Kunz-Ebrecht S, Mohamed-Ali V. Inflammatory cytokines, socioeconomic status, and acute stress responsivity. Brain Behavior Immun. 2002;16:774–784.
14.
Edwards KM, Burns VE, Ring C, Carroll D. Sex differences in the interleukin-6 response to acute psychological stress. Biol Psychol 2006;71:236–239.
15.
Ferguson JF, Patel PN, Shah RY, et al. Race and gender variation in response to evoked inflammation. J Transl Med. 2013;11:63.
16.
Prather AA, Carroll JE, Fury JM, et al. Gender differences in stimulated cytokine production following acute psychological stress. Brain Behavior Immunity Special Issue Gender Ethnicity Immun. 2009;23:622–628.
17.
Verma R, Balhara YPS, Gupta CS. Gender differences in stress response: Role of developmental and biological determinants. Ind Psychiatry J. 2011;20:4–10.
18.
Goel N, Workman JL, Lee TT, Innala L, Viau V. Sex differences in the HPA axis. Comp Physiol. 2014;4:1121–1155.
19.
Lundberg U. Stress hormones in health and illness: The roles of work and gender. Psychoneuroendocrinolog. 2005;30:1017–1021.
20.
Pitychoutis PM, Papadopoulou-Daifoti Z. Of depression and immunity: Does sex matter? Int J Neuropsychopharmacol. 2010;13:675–689.
21.
Marmot M, Brunner E. Cohort Profile: The Whitehall II study. Int J Epidemiol. 2005;34:251–256.
22.
Hamer M, O’Donnell K, Lahiri A, Steptoe A. Salivary cortisol responses to mental stress are associated with coronary artery calcification in healthy men and women. Eur Heart J. 2010;31:424–429.
23.
Hackett RA, Hamer M, Endrighi R, Brydon L, Steptoe A. Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women. Psychoneuroendocrinolog. 2012;37:1801–1809.
24.
Stringhini S, Batty GD, Bovet P, et al. Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: The Whitehall II prospective cohort study. PLoS Med. 2013;10:e1001479.
25.
Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. J Appl Psychol Measure. 1977;1:385–401.
26.
Fagundes CP, Glaser R, Hwang BS, Malarkey WB, Kiecolt-Glaser JK. Depressive symptoms enhance stress-induced inflammatory responses. Brain Behav Immun. 2013;31:172–176.
27.
Hamer M, Steptoe A. Association between physical fitness, parasympathetic control, and proinflammatory responses to mental stress. Psychosom Med. 2007;69:660–666.
28.
Singh-Manoux A, Hillsdon M, Brunner E, Marmot M. Effects of physical activity on cognitive functioning in middle age: Evidence from the Whitehall II prospective cohort study. Am J Public Health. 2005;95:2252–2258.
29.
Vgontzas AN, Bixler EO, Lin HM, et al. IL-6 and its circadian secretion in humans. Neuroimmunomodulation. 2005;12:131–140.
30.
Zoccola PM, Figueroa WS, Rabideau EM, Woody A, Benencia F. Differential effects of poststressor rumination and distraction on cortisol and C-reactive protein. Health Psychol. 2014;33:1606–1609.
31.
Ramsay SE, Morris RW, Whincup PH, et al. Socioeconomic inequalities in coronary heart disease risk in older age: Contribution of established and novel coronary risk factors. J Thromb Haemost. 2009;7:1779–1786.
32.
Akinbami LJ, Moorman JE, Liu X. Asthma prevalence, health care use, and mortality: United States, 2005–2009. Natl Health Stat Report. 2011:1–14.
33.
McCallister JW, Holbrook JT, Wei CY, et al. Sex differences in asthma symptom profiles and control in the American Lung Association Asthma Clinical Research Centers. Respir Med. 2013;107:1491–1500.
34.
Chen E, Miller GE. Stress and inflammation in exacerbations of asthma. Brain Behav Immun. 2007;21:993–999.
35.
Ritz T, Steptoe A, DeWilde S, Costa M. Emotions and stress increase respiratory resistance in asthma. Psychosom Med. 2000;62:401–412.
36.
Rosenblat JD, Cha DS, Mansur RB, McIntyre RS. Inflamed moods: A review of the interactions between inflammation and mood disorders. Progress Neuro-Psychopharmacol Biological Psychiatr. 2014;53:23–34.
37.
Shivers KY, Amador N, Abrams L, et al. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity. Cytokine. 2015;72:121–129.
38.
Mohamed-Ali V, Bulmer K, Clarke D, et al. beta-Adrenergic regulation of proinflammatory cytokines in humans. Int J Obes Relat Metab Disord. 200;24 Suppl 2:S154–S155.
39.
Path G, Bornstein SR, Gurniak M, et al. Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: Increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function. J Clin Endocrinol Metab. 2001;86:2281–2288.
Metadata
Title
Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men
Authors
Romano Endrighi, PhD
Mark Hamer, PhD
Andrew Steptoe, DPhil
Publication date
01-08-2016
Publisher
Springer US
Published in
Annals of Behavioral Medicine / Issue 4/2016
Print ISSN: 0883-6612
Electronic ISSN: 1532-4796
DOI
https://doi.org/10.1007/s12160-016-9783-y

Other articles of this Issue 4/2016

Annals of Behavioral Medicine 4/2016 Go to the issue

Original Article

Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial

Brief Report

Unintended Effects of a Smoking Cessation Intervention on Latino Fathers’ Binge Drinking In Early Postpartum

Original Article

Goal Navigation, Approach-Oriented Coping, and Adjustment in Young Men with Testicular Cancer

Original Article

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study

Original Article

Expectancy Effects on Conditioned Pain Modulation Are Not Influenced by Naloxone or Morphine

Original Article

Mind the Gap? An Intensive Longitudinal Study of Between-Person and Within-Person Intention-Behavior Relations