Tumor Necrosis Factor Production and Accumulation of Inflammatory Cells in the Corpus Luteum of Pseudopregnancy and Pregnancy in Rabbits1

The potential involvement of macrophages, T lymphocytes, and the cytokine twnor necrosis factor (TNF) in regression of the corpus hueum was investigated at d(fferent stages of pseudopregnancy and pregnancy by use of immunocytochemical methods and a TNF bioassay. Few macrophages (11± 6per high power field of 8-j.un frozen sections of corpus luteum, Day 10 of pseudopregnancy) were observed until the very end of pseudopregnancy, when the number of macrophages increased greatly (176 ± 42 per high power field, Day 19 ofpseudopregnancy). Pregnancy, of 32 days duration, delayed large-scale macrophage accumulation until 3 days after parturition (154 ± 30 per high powerfield). Low TNF activity (-1.0 U/mg protein) was detected in incubations of luteal tissue ala!! stages; in response to lipopolysaccharide, TNF values in medium increased 10- to 30-fold at times of luzea! regression and macrophage accumulation (1 day postpartum and Day 19 ofpseudopregnancy). Class 11-positive T lymphocytes were observed in luteal tissue, but unlike macrophages, the number of lymphocytes did not increase at the time of regression of the corpus luteum. These data are consistent with the hypothesis that involution of the corpus lutewn is promoted through the interactions of inflammatory cells and action of TNF, although the action of TNF has not been determined in this luteal tissue. Through unknown mechanisms, pregnancy postpones the accu,nulation of macrophages in the corpus luteum, in association with the prolongation of luteal function until