CYTOKINE-LEUKOCYTE NETWORKS AND THE ESTABLISHMENT OF PREGNANCY

PROBLEM: Factors in seminal plasma stimulate an intense but transient inflammatory response in the murine endometrium at mating. The dim of our current studies is to delineate the cytokine-leukocyte interaction s comprising this response and to elucidate the significance of these events in changes in the maternal immune system and as determinants of pregnancy outcome. METHOD: We have reviewed our recent findings. RESU LTS: Transforming growth factor (TGF)-beta(1) has been identified as t he inflammation-inducing moiety in seminal plasma. Seminal TGF beta(1) initiates endometrial leukocyte infiltration by up-regulating epithel ial cell expression or granulocyte-macrophage colony-stimulating Facto r. Other cytokines and chemokines including regulated and normal T-cel l expressed and secreted (RANTES), macrophage inflammatory protein (MI P)-1 alpha, MIP-1 beta, and monocyte chemotactic protein-1 are also im plicated as mediators of macrophage and granulocyte recruitment and ac tivation. One consequence of this inflammatory response is the inducti on of a transient slate of hyporesponsiveness to paternal major histoc ompatibility class I antigens. CONCLUSION: Our studies suggest that se men may play a critical role in providing the antigenic and environmen tal signals necessary to initiate an appropriate maternal immune respo nse to the conceptus during pregnancy.