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IL-12, TNF-, and Hormonal Changes during Late Pregnancy and Early Postpartum: Implications for Autoimmune Disease Activity during These Times

Arthritis and Rheumatism Branch (I.J.E., R.L.W., M.C., K.S.K.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pediatric and Reproductive Endocrinology Branch (I.J.E., A.A.L., S.F., G.P.C.), National Institute of Child Health and Human Development, Developmental Endocrinology Branch (V.K.B.), National Institute of Child Health and Human Development, and Laboratory of Experimental and Computational Biology (M.D.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Ilia J. Elenkov, Division of Rheumatology, Immunology, and Allergy, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, D.C. 20007-2197. E-mail: ije{at}gunet.georgetown.edu

Abstract

Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset, in the postpartum period. The immune basis for these phenomena is poorly understood. Recently, excessive production of IL-12 and TNF- was causally linked to rheumatoid arthritis and multiple sclerosis. We studied 18 women with normal pregnancies in their third trimester and during the early postpartum period. We report that during the third trimester pregnancy, ex vivo monocytic IL-12 production was about 3-fold and TNF- production was approximately 40% lower than postpartum values. At the same time, urinary cortisol and norepinephrine excretion and serum levels of 1,25-dihydroxyvitamin were 2- to 3-fold higher than postpartum values. As shown previously, these hormones can directly suppress IL-12 and TNF- production by monocytes/macrophages in vitro. We suggest that a cortisol-, norepinephrine-, and 1,25-dihydroxyvitamin-induced inhibition and subsequent rebound of IL-12 and TNF- production may represent a major mechanism by which pregnancy and postpartum alter the course of or susceptibility to various autoimmune disorders.

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