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Interleukin-6 and Antiphospholipid Antibodies in Women With Contraceptive-Related Thromboembolic Disease

Barbara Salobir, MD, PhD and Mio abovi, MD, PhD

From the Department of Vascular Diseases, University Medical Centre, Ljubljana, Slovenia.

Address reprint requests to: Professor Mio abovi, MD, PhD, University Medical Centre, Department of Vascular Diseases, Zaloka 7, 1000 Ljubljana, Slovenia; e-mail: miso.sabovic{at}trnovo.kclj.si and miso.sabovic{at}volja.net.

OBJECTIVE: The aim of this study was to explore the possible (joint) contributing role of interleukin-6 (IL-6) and antiphospholipid antibodies to the occurrence of the venous thromboembolism in women using oral contraceptives.

METHODS: Interleukin-6 and antiphospholipid antibodies (anti-ß2-glycoprotein I antibody–immunoglobulin M [IgM], G [IgG], and A [IgA]; anticardiolipin-IgM and IgG; antiphosphatidylserine-IgM and IgG) were measured in 30 women (median age 41, range 28–49 years) in the stable period (on average 3.5 years) after first venous thromboembolism. Sixteen patients used oral contraceptives during the episode of venous thromboembolism (oral contraceptives group), whereas 14 patients did not (non–oral contraceptives group). Thirty-seven age-matched, healthy women served as controls

RESULTS: Compared with controls, the oral contraceptives group had elevated IL-6 (median interquartile range 2.3 [1.1–4.3] versus 1.4 [0–2.0] pg/mL, P < .05). The oral contraceptives group had elevated anti-ß2-glycoprotein I antibody–IgM in comparison with both the non–oral contraceptives group (median interquartile range 47.5 [2.0–77.0] versus 29.50 [11.00–45.50] OD₄₅₀, P < .06) and controls (47.5 [2.0–77.0] versus 17.5 [3.5–30.0] OD₄₅₀, P < .001). Interleukin-6 level in the non–oral contraceptives group was related to obesity, whereas such a relation was not found in the oral contraceptives group, suggesting the presence of another factor (oral contraceptive use), which stimulates IL-6 production. Of particular interest is our finding that elevated IL-6 levels correlated significantly positively with elevated anti-ß2-glycoprotein I antibody–IgG in patients who were users of oral contraceptives (but not overweight, n = 10) (r = 0.56, P < .05)

CONCLUSION: The results suggest a new hypothesis that, in susceptible women, use of oral contraceptives induces production of IL-6, which stimulates production of anti-ß2-glycoprotein I. Thus, the prothrombotic profile is aggravated and could facilitate occurrence of venous thromboembolism. This remains to be elucidated in further studies.

LEVEL OF EVIDENCE: III

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