Effect of pregnancy on serum cytokines in SLE patients

Abstract

IntroductionThe aim of this study was to evaluate an extensive panel of cytokines involved in immune regulation during pregnancy in patients with systemic lupus erythematosus (SLE) and in healthy women.MethodsA total of 47 consecutive successful pregnancies in 46 SLE patients and 56 pregnancies in 56 matched healthy subjects, as controls, were prospectively studied. Serum interleukin (IL)-1-α, IL-1-β, IL-2, IL-6, IL-8, IL-10, IL-12p70, interferon (INF)-γ and tumor necrosis factor (TNF)-α were detected in sera obtained at the first and third trimester of pregnancy by a highly sensitive, multiplexed sandwich ELISA.ResultsMedians (pg/ml) of serum levels of most helper T (Th)1-type cytokines were significantly lower in the third trimester compared with those observed in the first trimester of pregnancy in healthy women: INF-γ 2.0 vs 3.4, TNF-α 10.2 vs 11.5, IL-1-α 0.9 vs 1.1, IL-1-β 0.6 vs 1.0, IL-2 3.0 vs 3.5, and IL-12p70 4.9 vs 5.6 (P-values < 0.02 for all). By contrast, only the IL-1-α serum levels were lower in the third trimester compared with the first trimester in SLE patients (P = 0.006). IFN-γ/IL-6 and IFN-γ/IL-10 ratios were higher in controls than in SLE (P = 0.002, and P = 0.001, respectively); moreover, they were significantly reduced in the third compared to the first trimester of pregnancy in healthy women, but not in SLE.ConclusionsIn SLE patients, Th1/Th2 cytokine serum level ratio does not decrease during pregnancy progression as much as in healthy pregnant women. This could account for the observation of a low frequency of disease flares in the third trimester of gestation.

Modulation of cytokine patterns and microbiome during pregnancy in IBD

“…Normal pregnancy is associated with hormonal, microbial and immunological changes, which prepare the maternal body for successful childbirth. Interestingly, some autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, show improvement during pregnancy, while risk of flares increases postpartum 14–16. This suggests that pregnancy-induced physiological changes affect immune processes at peripheral sites, and it has been suggested that increased levels of Tregs and a shift towards Th2 cytokine patterns contribute to amelioration of Th1-driven diseases41 42 and conversely also play a role in exacerbation of Th2-driven inflammatory diseases such as systemic lupus erythematosus during pregnancy 43 44.…”

“…Successful implantation requires a proinflammatory Th1 environment at the maternal–fetal interface, which is followed by a shift towards a more tolerogenic Th2 response for the main duration of pregnancy, with again increased polarisation to a Th1 response shortly before partition 14 15. However, it is unclear to what extent placental immunological shifts actually translate to systemic immunological changes capable of affecting disease activity in the intestinal tract, as surprisingly few studies have investigated peripheral changes across the different trimesters of pregnancy, and those that did show conflicting results 16–18…”

Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

“…Successful pregnancy has previously been described as predominantly a type 2 immune response-biased phenomenon [ 34 – 36 ]. In light of the collective evidence, it seems that the description of pregnancy in terms of type 2 immune responses may be oversimplified, both in the overall description of key cytokines/growth factors as well as in the temporal dynamics, and it is in need of further refinement.…”

Estrogen’s effects in chronic autoimmune/inflammatory diseases and progression to cancer

“…In any case, the endocrine-immune interactions clearly play their fundamental role in pregnancy [34].…”