Study on nonspecific immunity in pregnant women: II. Effect of hormones on chemiluminescence response of peripheral blood phagocytes.

To analyze the mechanisms of increased nonspecific immunity in pregnant women, the effect of various hormones on the phagocytic activity was estimated by a luminol-dependent chemiluminescence (CL) response during phagocytosing opsonized zymosan. The CL response of whole blood supplemented with exogenous human chorionic gonadotropin (hCG) increased significantly in all the male and female subjects and pregnant women. An approximate two- to fourfold increase was observed in comparison with the unsupplemented control in each subject at concentrations ranging from 1 to 1,000 IU/ml after 48 h of incubation (P less than 0.05). Progesterone slightly stimulated the CL response in female subjects only, but had no effect on male and pregnant women. Estradiol (E2) did not stimulate the CL response in any subject. The expression of Fc and C3b receptors on the surface of polymorphonuclear leucocytes (PMNL) in pregnant women was also investigated by measuring the immunofluorescence stained with monoclonal antibody to Fc and C3b receptors, respectively. The relative numbers of Fc receptors increased significantly in the third trimester compared to those of female control (P less than 0.05). Those of C3b receptor also increased in the second and third trimester (P less than 0.005). These results suggested that the nonspecific immunity represented by phagocytic activity in pregnant women increased with both oxidative metabolic responsiveness and the expression of membrane receptors. Besides, the increased phagocytic activity of the maternal host is probably due to the stimulatory effect of both endogenous and exogenous hCG on their peripheral blood phagocytes.

Influence of thyroid function on serum bone Gla protein.

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.

Study on nonspecific immunity in pregnant women: increased chemiluminescence response of peripheral blood phagocytes.

The total number of circulating leucocytes in the peripheral blood of pregnant women progressively increased with advance in gestation because of neutrophilia. When the phagocytic activity, representing nonspecific immunity, was estimated by a luminol-dependent chemiluminescence (CL) response during phagocytosing opsonized zymosan, we observed that the CL response of whole blood and Ficoll-Paque separated polymorphonuclear leucocytes (PMNL) significantly increased throughout the pregnancy (P less than 0.01). The CL responses of mononuclear leucocytes (MN) and monocytes also increased and reached peak levels in the third trimester (P less than 0.05). These findings suggest that the phagocytic activity in pregnant women increases, not only with regard to the number of phagocytes but also with regard to individual cell function, from a relatively early stage of the pregnancy, and that this increased nonspecific immunity may compensate in part for a weakened specific immunity of the maternal host. Attention should be directed to effects of human chorionic gonadotropin (hCG) relative to the increased CL response during pregnancy.

Prostaglandin modulation of the postnatal development of T and B lymphocytes in the spleens of newborn mice.

The effects of prostaglandin E2 (PGE2) on postnatal development of the T and B cells in the spleen were studied to investigate the relationship between in vivo PG concentration and immunological development of peripheral lymph organs after birth. The development of the T and B cells were suppressed by the PGE2 injection, while augmented by the indomethacin injection. Especially in the T cells, cellular immigration from the thymus to the spleen was suppressed by the PG injection. Therefore, in vivo PG concentration in postnatal period might have some affect on the development of peripheral lymph organs, and the cellular traffic from central to peripheral lymph organs.

Effects of immunization of mothers on the immune reaction of their offspring. II. Significance of enhanced antigen elimination by maternal antibodies on the suppression of the offspring.

In the offspring of sheep erythrocyte (SRBC)- or chicken erythrocyte (CRBC)-immunized mothers, generation of cytotoxicity and plaque forming cells (PFC) were suppressed, while delayed-type hypersensitivity (DTH) was not. We performed experiments to analyse the mechanism of this suppression. Antigen specific antibodies, which enhanced opsonization or antibody-dependent cell-mediated cytotoxicity (ADCC), might have a close relation to the suppression (1). The suppression was weakened by a high-dose of antigen challenge or macrophage blockade with colloidal carbon, while enhanced by macrophage activation with Corynebacterium parvum. In contrast, secondary immune responses in the offspring showed the same amplitude as in normal mice. Therefore, the suppression in the offspring might be a result from the early antigen elimination by enhanced opsonization or ADCC due to passive antibodies. But, generation of memory cells or effector cells of DTH might not be affected in the presence of passively transferred antibodies.

Effects of immunization of mothers on the immune reaction of their offspring: inhibition of immune responses of offspring caused by antibody imported through the milk.

Effects of immunization of pregnant AKR mice with nucleated chicken erythrocytes (CRBC) on immune responses of their offspring were examined. Antigen-specific reduction of generation of cytotoxicity and plaque forming cells (PFC) was demonstrated in the offspring at 8 weeks after birth, and lasted for 15 weeks. Cross-fostering experiments and cell transfer experiments showed that such suppression would be induced by antibody contained in the milk of immunized mothers rather than suppressor cells. Activities to enhance opsonization and to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) were demonstrated in the serum of such offspring before challenge with CRBC. Delayed footpad reaction (DFR) was maintained at the normal level in such offspring of immunized mice.

[Laboratory and clinical studies of cefotiam in digestive diseases].

Experimental and clinical studies on cefotiam (CTM), a new synthetic cephalosporin, were performed in digestive diseases. Among the 7 cases of 'cholelithiasis and cholangitis', 6 cases (86%) showed better response than "effective". Among the 9 cases of infections except 'cholelithiasis and cholangitis' which had no connection with cancers, 6 cases (67%) showed better response than "effective". Among the 15 cases of 'infections following advanced cancers', 7 cases (47%) showed better response than "effective". This inferior result was due to the relation to factors coming from cancers. CTM was effective in not only infections of the aged but that which resisted antibiotics of penicillins and the other cephems. Sensitivity of E. coli, Klebsiella and S. aureus was made a comparative study of by MIC and disc test. It was found as a result that CTM had the equal or superior antimicrobial activity to other antibiotics of cephems, penicillins and aminoglycosides.