In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy.
BACKGROUND
Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines; interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma during normal pregnancy.


METHODS
In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls.


RESULTS
The numbers of IFN-gamma and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-alpha and IL-10.


CONCLUSIONS
Our studies demonstrated increased numbers of both IFN-gamma and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-gamma on systemic immunity during pregnancy.
Matthiesen
Leif
L
The Division of Obstetrics and Gynaecology, Faculty of Health Sciences, University Hospital, S-581 85 Linköping, Sweden. leif.matthiesen@lio.se
Khademi
Mohsen
M
Ekerfelt
Christina
C
Berg
Göran
G
Sharma
Surendra
S
Olsson
Tomas
T
Ernerudh
Jan
J
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011247:Pregnancy / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma