Inhibition of interleukin-10 during pregnancy results in neonatal growth retardation.

PROBLEM: Interleukin 10 is considered to be important in the survival of the fetus in murine pregnancies that are known to be at risk for fetal wastage. The function of IL-10 in a normal pregnancy is not known. METHODS: In this report, we attempted to neutralize Interleukin 10 by administering anti IL-10 monoclonal antibodies (mAb) to pregnant mice that have a low background risk for fetal resorptions. The first group of mice was sacrificed on gestation day 18 to study the fetal effects of anti IL-10 administration. The second group of mice was allowed to deliver to study the effects on the neonatal outcome. RESULTS: Administration of anti IL-10 mAb did not affect the duration of gestation or the fetal outcome. Neonates exposed to anti IL-10 mAb in utero showed signs of transient growth deficiency starting at 4 weeks of age that spontaneously corrected by 6 weeks of age. CONCLUSIONS: Administration of anti IL-10 mAb does not alter the duration of gestation or the fetal outcome in normal murine pregnancies; however, it appears to be associated with transient neonatal growth problems.

Estrogen blocks early T cell development in the thymus.

PROBLEM: Pregnancy and estrogen are known to suppress B lymphopoiesis as well as lead to thymic involution in the mouse. Additionally, estrogen deficiency by oophorectomy reportedly causes a selective increase in the B220+ B cells in the murine bone marrow. The purpose of this study was to determine if estrogens played a regulatory role in T cell development. METHODS: The first experimental group consisted of 5-6-week-old Balb/c mice that received subcutaneous pellets of placebo, estriol, estradiol, or progesterone. The thymus glands were examined 2-4 weeks after treatment. The second group consisted of 6-week-old Balb/c mice who underwent either bilateral oophorectomy or a sham procedure. Two weeks after the surgery, extensive phenotypic characterization of the thymus and spleen cells was performed by flow cytometry using monoclonal antibodies to surface markers of T cell subsets. RESULTS: Estrogen treatment causes a dramatic reduction of thymic size and cellularity. All defined T cell subsets of CD4 and CD8 were reduced, with a disproportionate loss of CD4+CD8+ double positive cells. Examination of the triple negative (CD3-CD4-CD8-) subset revealed a striking loss of TN developmental progression of the early precursor cells. Based on the expression of CD44 (pgp-1) and CD25 (IL-2R alpha) markers, the TN thymic compartment was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; CD44-, CD25-) depleted. In contrast, all T cell developmental stages in the thymus were found to be in normal proportions in the oophorectomized mice, with no differences in the splenic T and B cell subsets. CONCLUSIONS: The study demonstrates that estrogen but not progesterone blocks T cell development in the thymus. However, contrary to our expectation, estrogen deprivation by oophorectomy does not enhance T cell development.

Effect of pregnancy on thymic T cell development.

PROBLEM: The thymus gland decreases in size during pregnancy. The significance of this alteration is not known. METHOD: In this report, we examined thymic function by evaluating the development of T lymphocytes in the thymus of pregnant Balb/c mice at 15 and 20 days gestation using multi-color flow cytometry. Comparative analysis was made with non-pregnant mice, post-partum lactating mice, and postpartum non-lactating mice. RESULTS: Progressive reduction of thymic size and cellularity during pregnancy was observed. All of the CD4 and CD8 defined subsets were reduced, with a disproportionate loss of CD4+, CD8+ double positive cells. Examination of the CD4-, CD8- double negative compartment revealed a predominance of TCR alpha, beta+ double negative cells, and a striking loss of precursor cells. The CD3-, CD4-, CD8- triple negative thymic subset was composed almost entirely of the earliest population (CD44+, CD25-), with the remaining maturational stages (CD44+, CD25+; CD44-, CD25+; and CD44-, CD25-) depleted. At 2 weeks postpartum, the subset ratios normalized, and the total cell count showed recovery. CONCLUSION: T cell development is blocked at the precursor level during the mouse pregnancy. These effects are transient, and gradual recovery is observed in the postpartum period.

Prolactin and plasma prostaglandin metabolite levels in patients undergoing nipple stimulation contraction stress tests.

Twenty-five patients undergoing nipple stimulation contraction stress tests were enrolled in this study. Plasma 13,14-dihydro, 15-keto prostaglandin F2 alpha and plasma prolactin concentrations were analyzed before and during the contraction stress tests. Prolactin concentrations were significantly higher (p less than 0.01) in patients who responded with a successful stress test versus those who did not. No significant changes were observed in the mean concentration of plasma 13,14-dihydro, 15-keto prostaglandin F2 alpha levels between the two groups.

Fetal anomalies associated with an inversion duplication 13 chromosome.

We report the cytogenetics and pathology of a fetus with holoprosencephaly associated with an inversion duplication 13 chromosome. The pathology is compared with that found in cases of partial duplication (trisomy) and deficiency (monosomy) of chromosome 13 described in the literature. To our knowledge, this is the first time holoprosencephaly has been associated with this particular inversion duplication 13 chromosome. Careful pathology and complete chromosomal studies proved useful in counseling this couple.