IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: Implications for autoimmune disease activity during these times

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