Challenging the TH1/TH2 Paradigm of Pregnancy

Challenging the TH1/TH2 Paradigm of Pregnancy

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Objective: There is a complement of cell types at the maternal-fetal interface, including, trophoblast, immune cells, decidual cells, and endothelial cells. The success of a pregnancy depends on how well the trophoblast responds/adapts to this environment. Mediators between these cell types include cytokines, growth factors and chemokines. We hypothesize that each trimester of a normal pregnancy is characterized by a unique and specific cytokine, chemokine and growth factor profile. This profile represents the process of adaptation of the mother to the presence of the fetus as well as the fetus to the maternal signals. Therefore, alterations in this process could be identified in the peripheral blood of the mother. Our objective was to establish a trimester specific protein profile.

Study Design: We obtained 1st, 2nd and 3rd trimester serum samples from women who completed a normal pregnancy. Using a cytokine micro array, we screened these samples for 60 proteins. Results from the cytokine micro arrays were validated using ELISA and Luminex.

Results: Trimester specific predominant protein profiles were as follows: 1st trimester - pro imflammatory, 2nd trimester - anti inflammatory and 3rd trimester - pro inflammatory.

Conclusion: These results challenge the TH1/TH2 paradigm of pregnancy, as a switch to a predominate TH2 environment did not occur until the 2nd trimester. Furthermore, this switch was not permanent as the 3rd trimester serum samples showed a pro inflammatory profile. We believe that the pro inflammatory protein profile seen in the 1st trimester serums is necessary for implantation/placentation while the pro inflammatory profile seen in the 3rd trimester samples is necessary for the initiation of labor. Thus, it may be too simplistic to regard pregnancy as a pure switch to a TH2 immunological environment. Instead, our findings suggest that normal pregnancy is a balance and interplay between TH1 and TH2 activity.


0002-9378/$ - see front matter
American Journal of Obstetrics and Gynecology
Volume 195, Issue 6, Supplement S (December 2006)
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