Azithromycin prevents pregnancy loss: reducing the level of tumor necrosis factor-alpha and raising the level of interleukin-10 in rats.

The aim of this study was to determine the effect of azithromycin on LPS-induced pregnancy loss. Thirty-six pregnant female Wistar rats were divided into 4 equal groups as follows: control group, where 0.3 mL of normal saline solution was administered intravenously on day 10 of pregnancy; azithromycin group, where azithromycin was administered orally at 350 mg kg(-1) day on days 9, 10, and 11 of pregnancy; lipopolysaccharide group, where LPS was administered intravenously via the tail vein at 160 µg kg(-1) on day 10 of pregnancy; and the azithromycin + LPS group, where azithromycin was administered orally at 350 mg kg(-1) day on days 9, 10, and 11 of pregnancy and LPS was administered intravenously at 160 µg kg(-1) on day 10 of pregnancy. Blood samples were obtained from the tail vein on day 10 of the experiment. Pregnancy rates were determined. Tumor necrosis factor-alpha (TNF- α ) and interleukin (IL-10) levels were measured by ELISA. Azithromycin prevented (P < 0.05) LPS-induced pregnancy loss. Higher TNF- α and IL-10 levels were measured (P < 0.05) in the LPS and azithromycin + LPS groups, respectively. In conclusion, azithromycin may be useful in infection- or endotoxemia-dependent pregnancy loss.

Inflammatory agents involved in septic miscarriage.

Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormalities has improved, there is a dearth of knowledge of the causes of loss in euploid conceptuses. Maternal infections are a cause of abort in humans, but the mechanisms are not clear, so we have developed a murine model to study the mechanism of septic abortion by inducing embryonic resorption (ER) with lipopolysaccharide (LPS). We demonstrated that augmented production of nitric oxide (NO) and prostaglandins (PG) is involved in ER, and that inhibitors of their synthesis could prevent ER. Also, we observed an increase in the oxidative damage, evidenced by nitration of tyrosine proteins, due to the peroxynitrite anion. Since an association between chronic marijuana smoking and early miscarriage has been shown in women, we studied the participation of anandamide (AEA), the principal endocannabinoid, on the mechanism of action of LPS. We showed that LPS-induced NO synthesis and tissue damage were mediated by AEA, and that this endotoxin inhibited AEA degradation and increased its synthesis. These results suggest that several inflammatory molecules participate in the mechanism of early pregnancy loss and that their modulation could be useful tools to prevent it.

Evaluation levels of cytokines in amniotic fluid of women with intrauterine infection in the early second trimester.

Amniotic fluid was obtained from 180 patients by amniocentesis at 16-22 weeks of gestation and assayed for the levels of interleukin (IL)-6, IL-8, leukocyte elastase (LE), and glucose. Ten of cases had clinical symptoms, such as uterine contraction, genital bleeding, and cervical ripening, and the other 170 were assessed for fetal chromosomal features. Four of the ten cases with uterine contraction developed abortion, while 10 of those screened had findings of fetal chromosomal anomalies, and 7 cases then underwent induced abortion artificially. In the cases of abortion, levels of IL-6, IL-8 and LE were higher than in the samples from the 160 pregnant women without clinical symptoms and a normal karyotype, while glucose in amniotic fluid was lower. Of 6 cases with clinical symptoms, but not developing abortion, 4 developed preterm labor, and in these IL-6 and IL-8 also were significantly elevated, with LE being slight high compared to normal. The results suggest that IL-6, IL-8, LE, and glucose in amniotic fluid at early second trimester can be used as markers of severe infection in the uterus, and with the first two being particularly sensitive.

Immune regulation during pregnancy and host-pathogen interactions in infectious abortion.

The immunological mechanisms that govern the success of pregnancy in outbred mammals are complex. During placental formation the invasion of fetal cells into maternal tissue must be controlled to prevent damage to the mother. Equally, maternal recognition of pregnancy must be such that allorejection of the fetus does not occur. Despite the complexity of this phenomenon, it is clear that cytokines play a crucial role at the maternofetal interface and in the periphery to ensure that pregnancy proceeds successfully. Inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) can exert detrimental effects in the placenta and tend to be present at low concentrations, whereas the regulatory cytokines interleukin (IL)-10 and tranforming growth factor-beta (TGF-beta) are beneficial and tend to predominate. This means that infection with pathogens that target the placenta and that elicit inflammatory responses may cause abortion by giving rise to a detrimental combination of cytokines that causes damage but does not control the disease. Infectious abortion is discussed in the context of the modulation of host immune responses during pregnancy, taking into account the different placental structures present in human beings, rodents and ruminants.

[Serological reactivity of healthy and ill people in relation to antigens from Bacteroides-serotypes (author's transl)]. / Serologische Reaktivität von Gesunden, Kranken und Tumor-Kranken gegenüber Antigenen verschiedener Bacteroides-Serotypen.

We investigated sera of healthy and ill people with different diagnoses to their reactivity against antigens isolated from six serotypes A--E2 (subspecies) of Bacteroides fragilis in indirect hemagglutination tests. These investigations were conducted partly in Poland and partly in the Netherlands. - In many cases antibodies towards several serotypes of Bacteroides fragilis were present in the healthy. In the Netherlands we found antibodies towards serotypes C and E2; in Poland serotypes D and E1 seem to be predominant in the healthy, whereas some reactivity towards other serotypes also could be observed (see table 1). - Hemagglutinationtiters in sera of the ill were frequently increased. In these sera we found also reactivity towards serotypes which are absent or rare in the healthy (see tables 2, 4 and 5). Sera of patients with carcinoma or sarcoma displayed high titers and especially reactivity towards those serotypes which are absent or rare in the healthy (see tables 3, 4 and 5).