Correlation between synthesis of ?2-macroglobulin in hepatocytes and changes in serum cytokine levels in rats after infl ammatory stimulation

The time course of ?2-macroglobulin (?2M) synthesis in rat liver was investigated using immunohistochemistry. Furthermore, correlations between synthesis of ?2M in hepatocytes and interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1), which are considered to contribute to the production of ?2M, were evaluated. The presence of ?2M in the liver was investigated by immunohistochemistry, and serum levels of ?2M, IL-6 and CINC-1 were measured by enzyme-linked immunosorbent assay. ?2M was not detected in the liver before injection of turpentine oil. ?2M was detected throughout the liver at 12 hours after injection of turpentine oil, when high serum levels of IL-6 and CINC-1 were observed. ?2M was distributed mainly around the central vein of the liver at 36 hours. Only small amounts of ?2M were detected in the liver at 48 hours, when peak serum levels of ?2M were observed. Synthesis of ?2M in hepatocytes peaked long before peak ?2M serum levels were seen. In conclusion, ?2M was considered to be synthesized in response to stimulation by IL-6 and CINC-1

Propylthiouracil Is Teratogenic in Murine Embryos

Background: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods: We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results: When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss o

Susceptibility of TNF-alpha-deficient mice to Trypanosoma congolense is not due to a defective antibody response

C57BL/6 mice deficient in one or two copies of the gene for tumor necrosis factor alpha (TNF-alpha) were more susceptible to Trypanosoma congolense infection than their resistant, wild-type counterparts. The number of TNF-alpha genes was correlated with the capacity to control parasitaemia and with survival time. Absence of TNF-alpha resulted in a diminished capacity to form germinal centres in lymph nodes and spleen. Since germinal centres are involved in antibody production and affinity maturation, the susceptibility of the TNF-alpha-deficient mice could have been due to this secondary defect. Despite the lack of the germinal centres, the antibody responses to internal and exposed trypanosome antigens and to non-trypanosome antigens were not significantly different. Also the relative avidities measured in infected sera did not significantly differ between the two mouse strains. These data suggest that the role of TNF-alpha in control of T. congolense was not due to its role in the development of an antibody response