Pharmacological evaluation of the immunomodulatory FL-6 in induced chronic hepatitis in Wistar rats.

The aim of this study was to evaluate the pharmacological effect of FL-6, a new immunomodulatory drug, in chronic hepatitis immunologically induced in rats via porcine-serum (PS) administration. Thirty-two male Wistar rats (150 g) were divided into 4 experimental groups: (1) Control (PBS 0.5 ml 3-times per week for 8-week); (2) FL-6 (50 ng/kg 3-times per week for 4-week); (3) Hepatitis (PS 373 mg/kg twice per week for 8-week); and (4) Hepatitis + FL-6 (doses as above). Rats were sacrificed at the end of treatment. ALT, AST, ALP and gamma-GT activities, as well as IL-6 and IL-10 levels, were evaluated in serum samples. Glutathione and malondialdehyde were also analyzed. A morphological analysis of liver tissue was carried out. The hepatitis group showed an increase in ALT (1.44-fold), AST (1.28-fold), ALP (1.83-fold), gamma-GT (3.91-fold), IL-6 (2.6-fold) and IL-10 (7.1-fold) levels when compared with controls (p < 0.05). Histopathological analysis revealed an inflammatory response characterized by inflammatory infiltrates and liver damage, which was accompanied by a reduction of 74.8% in glutathione levels (p < 0.05). However, animals with hepatitis treated with FL-6 had a reduction of ALT activity (17.74%), as well as a reduction in IL-6 (24.21%) and IL-10 (30.91%) levels (p < 0.05). These animals showed a reduction in inflammatory response characterized by a decrease in inflammatory infiltrate at the hepatic parenchyma and portal structures; livers showed less damage and a reduction of necrotic and apoptotic hepatocytes. In conclusion, the treatment with FL-6 improved liver function and reduced the inflammatory marker in rats with chronic hepatitis induced by PS-administration.

Immunomodulatory properties of Mycoplasma pulmonis. II. Studies on the mechanisms of immunomodulation.

Mycoplasma infection affects the host's immune system in different ways. In this work, a kinetic approach was used to try to determine the mechanisms by which Mycoplasma cause these effects. Experiments were performed using Balb/c mice infected with Mycoplasma pulmonis and several immunological parameters were determined. It was found that at days 10 and 15 post-infection, there were significant changes in the percentages of CD4+ and CD8 + cells, in both peripheral blood and the thymus. Significant sequential increases in concentrations of both IFN-gamma and IL-4 were detected in sera, such that at day 15, there was a peak in IFN-gamma, concentration and at day 38, IL-4 concentration also peaked. By day 46, both IFN-gamma and IL-4 fell to control levels despite continued infection. Delayed hypersensitivity (DTH) was reduced in infected animals compared to non-infected controls. A small recovery in DTH was observed at day 30, which was reduced again by day 40. Altogether, the results show features of a transitional shift from Th1 to Th2 in animals that are ultimately immunologically incompetent (in both cellular and humoral immunity). It appears to be this state of incompetence that allows the microorganism to survive and thus provides an explanation for the chronic state of the disease, which is a characteristic of Mycoplasma infection.

Acetaldehyde increases the activity and gene expression of urokinase type plasminogen activator in a hepatic stellate cell line.

The aim of this study was to investigate the effect of acetaldehyde on the activity and expression of urokinase type plasminogen activator gene in a clone of hepatic stellate cells. CFSC-2G cells showed typical morphological changes of the stellate cell activation, which were accompanied by an increase in the amount of collagen with all doses of acetaldehyde used. The treatment of the cells with doses of 100 and 175 micromol/l acetaldehyde, produced an increase in the urokinase type plasminogen activator activity not only in the cell extract, but also in conditioned medium. However, the use of higher doses of acetaldehyde (250 and 350 micromol/l) produced an inhibitory effect on the urokinase type plasminogen activator activity. In contrast, the higher urokinase type plasminogen activator gene expression was observed with doses of 175, 250, and 350 micromol/l. Our results shown that acetaldehyde induced changes in synthesis, release, and expression of urokinase type plasminogen activator in CFSC-2G cells. Those findings suggest that the alterations in the synthesis and expression of the urokinase type plasminogen activator might be another event associated to the activation of hepatic stellate cell after exposure to hepatotoxic agents like-acetaldehyde. The role of urokinase type plasminogen activator in fibrogenesis was analyzed.