PIBF: the double edged sword. Pregnancy and tumor.
OBJECTIVE
The role of progesterone-dependent immunomodulation in the maintenance of normal pregnancy.


METHODS
In vitro and in vivo data on the effect that progesterone and its mediator progesterone-induced blocking factor (PIBF) exert on the immune functions of pregnant women are reviewed, together with clinical findings.


RESULTS
Activated pregnancy lymphocytes express progesterone receptors, which enable progesterone to induce a protein called PIBF. PIBF increases Th2 type cytokine production by signaling via a novel type of IL-4 receptor and activating the Jak/STAT pathway. PIBF inhibits phosholipase A2, thus reduces prostaglandin synthesis. PIBF inhibits perforin release in human decidual lymphocytes and reduces the deleterious effect of high NK activity on murine pregnancy. PIBF production is a characteristic feature of normal human pregnancy, and its concentration is reduced in threatened pregnancies. PIBF mRNA and protein are expressed in a variety of malignant tumors. Inhibition of PIBF synthesis increases survival rates of leukemic mice.


CONCLUSIONS
Progesterone-induced blocking factor is produced by pregnancy lymphocytes and also by malignant tumors. The PIBF-induced Th2-dominant immune response is favorable during pregnancy but might facilitate tumor growth by suppressing local antitumor immune responses.
Szekeres-Bartho
Julia
J
Department of Medical Microbiology and Immunology, Medical School, Pecs University, H-7643 Pecs, Hungary. julia.szekeres@aok.pte.hu
Polgar
Beata
B
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D056747:Immunomodulation; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D011247:Pregnancy / Q000276:immunology*; D011257:Pregnancy Proteins / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D011980:Receptors, Progesterone / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000502:physiology*
D016207:Cytokines; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D011980:Receptors, Progesterone; D013491:Suppressor Factors, Immunologic; D016718:Arachidonic Acid; D011374:Progesterone; D054467:Phospholipases A2