Inhibition of dipeptidyl peptidase IV (DP IV, CD26) activity abrogates stress-induced, cytokine-mediated murine abortions

In the CBA x DBA/2 mouse model, stress-triggered abortions are mediated by a Th1-like cytokine response of decidual lymphocytes. The factors that dete rmine the cytokine pattern leading to abortion are currently unknown. Dipep tidyl 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 t he 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 o f an inhibitor of DP IV activity, Ile-thiazolidide (20 mu mol/kg). On day 1 3 of gestation, the animals were sacrificed and the percentage of implants and abortions documented. CD26-positive lymphocytes in spleen and uterine d ecidua and the intracellular cytokines interferon (IFN)-gamma and interleuk in (IL)-10 were determined by flow cytometry. Stressed and nonstressed anim als receiving an inactive stereoisomeric form were used as controls. In mic e receiving the DP IV inhibitor, stress failed to boost the abortion rate ( 37.2% versus 13.6%, P < 0.01). IFN-<gamma> producing sills were increased i n 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, in dependent from DP IV inhibition.