Comparison of gamma interferon, tumor necrosis factor, and direct cell contact in activation of antimycobacterial defense in murine macrophages.

We compared the abilities of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and sensitized murine lymph node lymphocytes to activate syngeneic murine peritoneal macrophages to inhibit the growth of intracellular Mycobacterium bovis BCG in vitro. IFN-gamma could activate antimycobacterial defense only when added to macrophage cultures prior to their infection with BCG. TNF-alpha was without any effect. In contrast, BCG-sensitized lymphocytes could induce antimycobacterial defenses when added after macrophages had been infected with BCG. The cell-mediated effect required direct contact between effector lymphocytes and the targets (BCG-infected macrophages), as revealed in studies in which these cell populations were separated by a semipermeable membrane. Cyclosporin A, which inhibits the production of relevant macrophage-activating lymphokines, did not abrogate the ability of sensitized lymphocytes to activate antimycobacterial effects in infected macrophages. Furthermore, only BCG-sensitized lymphocytes, and not Listeria-sensitized lymphocytes, could activate the antimycobacterial effects. These lymphocytes were not cytotoxic to the infected macrophages. The presence of anti-TNF-alpha antibody in cocultures reduced the antimicrobial effects. We propose that the activation of antimycobacterial defense in macrophages can occur by direct physical contact with sensitized lymphocytes. This process may be due to lymphocyte membrane-associated TNF-alpha, as we previously demonstrated in our studies of antileishmanial defense.

The effects of hydrocortisone on the development of the amine systems in the fetal brain.

Human and animal studies suggest impaired central nervous system (CNS) development due to corticoid use in the perinatal period. In this study, hydrocortisone was given to pregnant rats and the development of the fetal dopamine (DA) and norepinephrine (NE) systems in the CNS was investigated. In the fetal rat brain DA and NE systems develop between days 12 and 17 of gestation. Hydrocortisone (HC), 57 mg/kg/day, or saline (SAL) was given intraperitoneally at day 12 or 15 of gestation. The offspring were studied at days 20 to 21 of gestation and days 12 to 13 in the neonatal period. Brain amine systems were visualized using a modified cryostat glyoxylic acid histofluorescence method, and DA and NE levels were determined in whole brains by means of a radioenzymatic assay. The visualized amine systems were evaluated semiquantitatively for distribution and fluorescence intensity without previous knowledge of the administered drug. The amine systems of the HC and SAL groups showed an equal maturation. In both groups cell bodies were demonstrable in areas A1 to A13 and axon terminals in all examined final regions. The distribution and the fluorescence intensity did not show consistent differences for the HC and SAL brains. The concentrations of DA and NE were similar in the offspring of the SAL- and HC-treated animals. The results indicate that HC given during pregnancy does not influence the proliferation of amine cell bodies or the arrival of axon terminals in the regions where the synapses form.