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Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum

M Østensen¹, F Förger¹, J L Nelson², A Schuhmacher³, G Hebisch⁴, P M Villiger¹

¹ Department of Rheumatology and Clinical Immunology and Allergology, University Hospital, Bern, Switzerland
² Fred Hutchinson Cancer Research Center, and the Division of Rheumatology, University of Washington, Seattle, Washington, USA
³ County Hospital of Belp, Switzerland
⁴ Department of Gynaecology at the University Hospital of Zürich, Switzerland

Correspondence to:
Professor M Østensen
Department of Rheumatology and Clinical Immunology and Allergy, University Hospital, CH-3010 Bern, Switzerland; monika.oestensen{at}insel.ch

Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS).

Methods: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon (IFN), interleukin (IL) 1ß, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines.

Results: Low levels of IL10 were found sporadically, whereas IFN and IL1ß were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy.

Conclusions: IFN and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity.

Abbreviations: AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Activity Index; CRP, C reactive protein; ELISA, enzyme linked immunosorbent assay; IFN, interferon ; IL, interleukin; IL1Ra, interleukin 1 receptor antagonist; JIA, juvenile idiopathic arthritis; NSAIDs, non-steroidal anti-inflammatory drugs; PGA, physician’s global assessment; RA, rheumatoid arthritis; RADAI, RA Disease Activity Index; sCD30, soluble CD30; sTNFR, soluble tumour necrosis factor receptor; TNF, tumour necrosis factor

Keywords: cytokines; immune response; pregnancy; rheumatic disease

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