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CLINICAL RESEARCH: ATHEROSCLEROSIS

Plasma Interleukin-5 Levels Are Related to Antibodies Binding to Oxidized Low-Density Lipoprotein and to Decreased Subclinical Atherosclerosis

Maritta Sämpi, MS^_*, Olavi Ukkola, MD, PhD^_*, Markku Päivänsalo, MD, PhD, Y. Antero Kesäniemi, MD, PhD^_*, Christoph J. Binder, MD, PhD and Sohvi Hörkkö, MD, PhD^,_*

^_* Department of Internal Medicine, Biocenter Oulu, Oulu, Finland
Department of Pharmacology and Toxicology, University of Oulu and Clinical Research Center of Oulu University Hospital, Oulu, Finland
Department of Radiology, University of Oulu, Oulu, Finland
Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

Manuscript received April 9, 2008; revised manuscript received June 3, 2008, accepted June 3, 2008.

^_* Reprint requests and correspondence: Dr. Sohvi Hörkkö, Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, P.O. Box 5000, Oulu, FIN-90014, Finland (Email: sohvi.horkko{at}oulu.fi).

Objectives: This study's aim was to assess the role of interleukin (IL)-5 in modulating the levels of antibodies binding to oxidized low-density lipoprotein (OxLDL) in human atherosclerosis.

Background: Various pro- and anti-inflammatory cytokines have been implicated in atherogenesis, and recent findings in mice indicate that the cytokine IL-5 plays a protective role in atherosclerosis in part via the induction of antibodies binding to OxLDL.

Methods: Plasma IL-5 levels and antibody titers to 2 most commonly used models of OxLDL (copper OxLDL and malondialdehyde-modified LDL) were measured in 1,011 Finnish middle-aged subjects with chemiluminescent enzyme-linked immunosorbent assay. Intima-media thickness (IMT) was assessed ultrasonographically from the internal carotid artery, the bifurcation, and the common carotid artery.

Results: There was a significant positive association between plasma IL-5 levels and antibody titers to copper OxLDL (p = 0.010 and p = 0.044, immunoglobin [Ig] M and G, respectively) and IgM to malondialdehyde-modified LDL (p < 0.001) in the association analysis performed between different IL-5 quartiles. Furthermore, plasma IL-5 levels were found to be inversely associated with bifurcational IMT, and even after adjustments for traditional risk factors of atherosclerosis (age, gender, smoking, systolic blood pressure, LDL, and body mass index), IL-5 remained an independent determinant of the mean bifurcational IMT (p = 0.010).

Conclusions: Our data demonstrate that plasma IL-5 levels are related to the plasma levels of antibodies binding to OxLDL and to decreased subclinical atherosclerosis in humans. These results are in line with earlier findings in murine atherosclerosis and indicate for the first time that IL-5 may play a role in human atherosclerosis.

Key Words: interleukin-5 • antibody • oxidized low-density lipoprotein • atherosclerosis

Abbreviations and Acronyms   BMI = body mass index   CuOx-LDL = copper oxidized low-density lipoprotein   Ig = immunoglobulin   IL = interleukin   IMT = intima-media thickness   LDL = low-density lipoprotein   LDLR = low-density lipoprotein receptor   MDA-LDL = malondialdehyde-modified low-density lipoprotein   PC = phosphocholine   OxLDL = oxidized low-density lipoprotein

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