Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2019

Open Access 01-12-2019 | Research article

Serum IL8 is not associated with cardiovascular events but with all-cause mortality

Authors: Ilais Moreno Velásquez, Ashwini Gajulapuri, Karin Leander, Anita Berglund, Ulf de Faire, Bruna Gigante

Published in: BMC Cardiovascular Disorders | Issue 1/2019

Login to get access

Abstract

Background

The aim of this study is to investigate if IL8 levels were associated with incident cardiovascular (CV) events (CVE) and mortality (all-cause, CV, and cancer) in a cohort of 60 years old men and women from Stockholm (60YO).

Methods

The 60YO comprises 4232 participants; baseline period: 1997–1999. The cohort is matched annually to population registries to record deaths and incident CVE. Serum IL8 was measured in 4011 participants and categorized in quartiles. Cox proportional hazard models were used to estimate the CVE and mortality risk, expressed as hazard ratios (HR) with 95% confidence intervals (CI). Potential confounding was addressed by adjusting for traditional CV risk factors (CVE estimates) and by sex, life style habits, metabolic factors (mortality estimates). Laplace regression was used to calculate the difference in time until a certain percentage of the cohort died according to IL8 levels.

Results

During 16.5 years follow up, 522 incident CVE were recorded and 647 study participants died. IL8 was not associated with CVE risk (IL8 Q4 vs Q1, HR of 0.95; 95% CI 0.75–1.22). Compared to Q1, IL8 Q4 was associated with all-cause mortality (adjusted HR 1.28; 95% CI 1.02–1.63). No association was observed with CV and cancer related mortality in the fully adjusted model. Participants with IL8 above the median died of any cause ≈1.3 years before the 15% of the population had died.

Conclusion

Elevated IL8 levels were not associated with CVE risk and CV mortality, but were associated with an increased risk of all-cause mortality regardless of the underlying cause.
Appendix
Available only for authorised users
Literature
1.
go back to reference Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. The Lancet Oncology. 2014;15:e493–503.CrossRef Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. The Lancet Oncology. 2014;15:e493–503.CrossRef
3.
go back to reference Gerszten RE, Garcia-Zepeda EA, Lim YC, et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature. 1999;398:718–23.CrossRef Gerszten RE, Garcia-Zepeda EA, Lim YC, et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature. 1999;398:718–23.CrossRef
4.
go back to reference Yue TL, Wang X, Sung CP, et al. Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells. Circ Res. 1994;75:1–7.CrossRef Yue TL, Wang X, Sung CP, et al. Interleukin-8. A mitogen and chemoattractant for vascular smooth muscle cells. Circ Res. 1994;75:1–7.CrossRef
5.
go back to reference Moreau M, Brocheriou I, Petit L, Ninio E, Chapman M, Rouis M. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation. 1999;99:420–6.CrossRef Moreau M, Brocheriou I, Petit L, Ninio E, Chapman M, Rouis M. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation. 1999;99:420–6.CrossRef
6.
go back to reference Schomig K, Busch G, Steppich B, et al. Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction. Eur Heart J. 2006;27:1032–7.CrossRef Schomig K, Busch G, Steppich B, et al. Interleukin-8 is associated with circulating CD133+ progenitor cells in acute myocardial infarction. Eur Heart J. 2006;27:1032–7.CrossRef
7.
go back to reference Simonini A, Moscucci M, Muller DW, et al. IL-8 is an angiogenic factor in human coronary atherectomy tissue. Circulation. 2000;101:1519–26.CrossRef Simonini A, Moscucci M, Muller DW, et al. IL-8 is an angiogenic factor in human coronary atherectomy tissue. Circulation. 2000;101:1519–26.CrossRef
8.
go back to reference Liu Q, Li A, Tian Y, et al. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016;31:61–71.CrossRef Liu Q, Li A, Tian Y, et al. The CXCL8-CXCR1/2 pathways in cancer. Cytokine Growth Factor Rev. 2016;31:61–71.CrossRef
9.
go back to reference Boekholdt SM, Peters RJ, Hack CE, et al. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study. Arterioscler Thromb Vasc Biol. 2004;24:1503–8.CrossRef Boekholdt SM, Peters RJ, Hack CE, et al. IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study. Arterioscler Thromb Vasc Biol. 2004;24:1503–8.CrossRef
10.
go back to reference Herder C, Baumert J, Thorand B, et al. Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Arterioscler Thromb Vasc Biol. 2006;26:2147–52.CrossRef Herder C, Baumert J, Thorand B, et al. Chemokines and incident coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Arterioscler Thromb Vasc Biol. 2006;26:2147–52.CrossRef
11.
go back to reference Velasquez IM, Frumento P, Johansson K, et al. Association of interleukin 8 with myocardial infarction: results from the Stockholm heart epidemiology program. Int J Cardiol. 2014;172:173–8.CrossRef Velasquez IM, Frumento P, Johansson K, et al. Association of interleukin 8 with myocardial infarction: results from the Stockholm heart epidemiology program. Int J Cardiol. 2014;172:173–8.CrossRef
12.
go back to reference Kostulas N, Kivisakk P, Huang Y, Matusevicius D, Kostulas V, Link H. Ischemic stroke is associated with a systemic increase of blood mononuclear cells expressing interleukin-8 mRNA. Stroke. 1998;29:462–6.CrossRef Kostulas N, Kivisakk P, Huang Y, Matusevicius D, Kostulas V, Link H. Ischemic stroke is associated with a systemic increase of blood mononuclear cells expressing interleukin-8 mRNA. Stroke. 1998;29:462–6.CrossRef
13.
go back to reference Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H. Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke. 1999;30:2174–9.CrossRef Kostulas N, Pelidou SH, Kivisakk P, Kostulas V, Link H. Increased IL-1beta, IL-8, and IL-17 mRNA expression in blood mononuclear cells observed in a prospective ischemic stroke study. Stroke. 1999;30:2174–9.CrossRef
14.
go back to reference Lippitz B. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14:e218–28.CrossRef Lippitz B. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14:e218–28.CrossRef
15.
go back to reference Moreno Velasquez I, Arnlov J, Leander K, Lind L, Gigante B, Carlsson AC. Interleukin-8 is associated with increased total mortality in women but not in men-findings from a community-based cohort of elderly. Ann Med. 2015;47:28–33.CrossRef Moreno Velasquez I, Arnlov J, Leander K, Lind L, Gigante B, Carlsson AC. Interleukin-8 is associated with increased total mortality in women but not in men-findings from a community-based cohort of elderly. Ann Med. 2015;47:28–33.CrossRef
16.
go back to reference Nymo SH, Hulthe J, Ueland T, et al. Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA. Eur J Heart Fail. 2014;16:68–75.CrossRef Nymo SH, Hulthe J, Ueland T, et al. Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA. Eur J Heart Fail. 2014;16:68–75.CrossRef
17.
go back to reference Baune BT, Rothermundt M, Ladwig KH, Meisinger C, Berger K. Systemic inflammation (interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO study. Age. 2011;33:209–17.CrossRef Baune BT, Rothermundt M, Ladwig KH, Meisinger C, Berger K. Systemic inflammation (interleukin 6) predicts all-cause mortality in men: results from a 9-year follow-up of the MEMO study. Age. 2011;33:209–17.CrossRef
18.
go back to reference Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.CrossRef Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.CrossRef
19.
go back to reference Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–42.CrossRef Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1833–42.CrossRef
20.
go back to reference Gigante B, Leander K, Vikstrom M, et al. Elevated ApoB serum levels strongly predict early cardiovascular events. Heart. 2012;98:1242–5.CrossRef Gigante B, Leander K, Vikstrom M, et al. Elevated ApoB serum levels strongly predict early cardiovascular events. Heart. 2012;98:1242–5.CrossRef
21.
go back to reference Nystrom PK, Carlsson AC, Leander K, de Faire U, Hellenius ML, Gigante B. Obesity, metabolic syndrome and risk of atrial fibrillation: a Swedish, prospective cohort study. PLoS One. 2015;10:e0127111.CrossRef Nystrom PK, Carlsson AC, Leander K, de Faire U, Hellenius ML, Gigante B. Obesity, metabolic syndrome and risk of atrial fibrillation: a Swedish, prospective cohort study. PLoS One. 2015;10:e0127111.CrossRef
22.
go back to reference Laguzzi F, Riserus U, Marklund M, Vikstrom M, Sjogren P, Gigante B, et al. Circulating fatty acids in relation to alcohol consumption: cross-sectional results from a cohort of 60-year-old men and women. Clin Nutr. 2018;37(6 Pt A):2001–10. Laguzzi F, Riserus U, Marklund M, Vikstrom M, Sjogren P, Gigante B, et al. Circulating fatty acids in relation to alcohol consumption: cross-sectional results from a cohort of 60-year-old men and women. Clin Nutr. 2018;37(6 Pt A):2001–10.
23.
go back to reference Romuk E, Skrzep-Poloczek B, Wojciechowska C, et al. Selectin-P and interleukin-8 plasma levels in coronary heart disease patients. Eur J Clin Investig. 2002;32:657–61.CrossRef Romuk E, Skrzep-Poloczek B, Wojciechowska C, et al. Selectin-P and interleukin-8 plasma levels in coronary heart disease patients. Eur J Clin Investig. 2002;32:657–61.CrossRef
24.
go back to reference Zhou RH, Shi Q, Gao HQ, Shen BJ. Changes in serum interleukin-8 and interleukin-12 levels in patients with ischemic heart disease in a Chinese population. J Atheroscler Thromb. 2001;8:30–2.CrossRef Zhou RH, Shi Q, Gao HQ, Shen BJ. Changes in serum interleukin-8 and interleukin-12 levels in patients with ischemic heart disease in a Chinese population. J Atheroscler Thromb. 2001;8:30–2.CrossRef
25.
go back to reference Persson J, Lindberg K, Gustafsson TP, Eriksson P, Paulsson-Berne G, Lundman P. Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med. 2010;268:194–205.CrossRef Persson J, Lindberg K, Gustafsson TP, Eriksson P, Paulsson-Berne G, Lundman P. Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med. 2010;268:194–205.CrossRef
26.
go back to reference Moreno Velasquez I, Kumar J, Bjorkbacka H, et al. Duffy antigen receptor genetic variant and the association with interleukin 8 levels. Cytokine. 2015;72:178–84.CrossRef Moreno Velasquez I, Kumar J, Bjorkbacka H, et al. Duffy antigen receptor genetic variant and the association with interleukin 8 levels. Cytokine. 2015;72:178–84.CrossRef
27.
go back to reference Marin V, Montero-Julian FA, Gres S, Boulay V, Bongrand P, Farnarier C. The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin. J Immunol. 2001;167:3435–42.CrossRef Marin V, Montero-Julian FA, Gres S, Boulay V, Bongrand P, Farnarier C. The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin. J Immunol. 2001;167:3435–42.CrossRef
28.
go back to reference Bruun JM, Lihn AS, Madan AK, et al. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Phys Endocrinol Metab. 2004;286:E8–13.CrossRef Bruun JM, Lihn AS, Madan AK, et al. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Phys Endocrinol Metab. 2004;286:E8–13.CrossRef
29.
go back to reference Stork S, Feelders RA, van den Beld AW, et al. Prediction of mortality risk in the elderly. Am J Med. 2006;119:519–25.CrossRef Stork S, Feelders RA, van den Beld AW, et al. Prediction of mortality risk in the elderly. Am J Med. 2006;119:519–25.CrossRef
30.
go back to reference Lefer AM, Johnson G 3rd, Ma XL, Tsao PS, Thomas GR. Cardioprotective and endothelial protective effects of [ala-IL8]77 in a rabbit model of myocardial ischaemia and reperfusion. Br J Pharmacol. 1991;103:1153–9.CrossRef Lefer AM, Johnson G 3rd, Ma XL, Tsao PS, Thomas GR. Cardioprotective and endothelial protective effects of [ala-IL8]77 in a rabbit model of myocardial ischaemia and reperfusion. Br J Pharmacol. 1991;103:1153–9.CrossRef
Metadata
Title
Serum IL8 is not associated with cardiovascular events but with all-cause mortality
Authors
Ilais Moreno Velásquez
Ashwini Gajulapuri
Karin Leander
Anita Berglund
Ulf de Faire
Bruna Gigante
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2019
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-019-1014-6

Other articles of this Issue 1/2019

BMC Cardiovascular Disorders 1/2019 Go to the issue