Macrophage Migration Inhibitory Factor in Human Pregnancy and Labor

PROBLEM: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in reproduction. Presently there is no information on the possible involvement of MIF in the onset of labor. METHODS: Macrophage migration inhibitory factor was assayed, by enzyme-linked immunosorbent assay (ELISA), in maternal serum (MS) and amniotic fluid (AF) both, at midtrimester and at term, as well as in cord serum (CS) at birth. Extraembryonic membranes were analyzed by immunohistochemistry. RESULTS: Amniotic fluid MIF concentrations were significantly higher at term (median 62.10 ng/mL) than at midtrimester (median 20.07 ng/mL) and reached a peak in term labor (median 258.80 ng/mL). The AF/MS ratio varied from a median of 4.34 at midtrimester and 33.7 at term labor. The MS/CS ratio was 0.4. Migration inhibitory factor immunoreactivity was found in different cell layers of the extraembryonic membranes. CONCLUSIONS: The increased secretion of MIF in AF at term, particularly at term labor, suggests that MIF contributes to the inflammatory events leading to labor

Cytokines and pregnancy in rheumatic disease

Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study