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Inhibition of Dipeptidyl Peptidase IV (DP IV, CD26) Activity Abrogates Stress‐Induced, Cytokine‐Mediated Murine Abortions
Author(s) -
Hildebrandt M.,
Arck P. C.,
Kruber S.,
Demuth H.U.,
Reutter W.,
Klapp B. F.
Publication year - 2001
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2001.00901.x
Subject(s) - cytokine , decidua , dipeptidyl peptidase , endocrinology , medicine , immunology , interferon gamma , andrology , biology , fetus , pregnancy , placenta , biochemistry , genetics , enzyme
In the CBA × DBA/2 mouse model, stress‐triggered abortions are mediated by a Th1‐like cytokine response of decidual lymphocytes. The factors that determine the cytokine pattern leading to abortion are currently unknown. Dipeptidyl Peptidase IV (DP IV) enhances Th1‐cytokine responses and impairs the evolvement of a Th2 cytokine profile. The T‐cell‐activation antigen, CD26, possesses DP IV activity. The aim of the present study was to investigate the role of DP IV activity and CD26‐positive decidual lymphocytes in murine stress‐triggered abortions by inhibition of DP IV activity. DBA/2‐mated CBA mice were stressed on day 5.5 of pregnancy and received daily injections of an inhibitor of DP IV activity, Ile‐thiazolidide (20 µmol/kg). On day 13 of gestation, the animals were sacrificed and the percentage of implants and abortions documented. CD26‐positive lymphocytes in spleen and uterine decidua and the intracellular cytokines interferon (IFN)‐γ and interleukin (IL)‐10 were determined by flow cytometry. Stressed and nonstressed animals receiving an inactive stereoisomeric form were used as controls. In mice receiving the DP IV inhibitor, stress failed to boost the abortion rate (37.2% versus 13.6%, P < 0.01). IFN‐γ producing cells were increased in stressed animals, but returned to the baseline upon the inhibition of DP IV. The number of IL‐10 producing cells was reduced in stressed animals, independent from DP IV inhibition.