oxazolone and Body-Weight

Since glycolipid biosynthesis is potentially involved in immunological and inflammatory responses, we tested the effect of a novel inhibitor of intracellular glycolipid biosynthesis N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) in two hapten-induced colitis models: trinitrobenzene sulphonic acid (TNBS)- and oxazolone (4-ethoxymethylene-2phenyl-2oxazoline-5-one; Oxa)-induced colitis. AMP-DNM was given either by intraperitoneal injection or orally via the diet. Mice treated with AMP-DNM had less severe colitis and a more rapid weight recovery, less edema and less wall thickness. Cellular infiltration, goblet cell loss and myeloperoxidase (MPO) activity were reduced in colons of AMP-DNM-treated animals. Intralesional IFN-gamma and IL-18 production were lower in mice of the AMP-DNM-treated groups. Furthermore, AMP-DNM treatment reduced the serum anti-TNBS and anti-Oxa antibody levels. Our findings show that the glycolipid biosynthesis inhibitor AMP-DNM has a strong anti-inflammatory and immune suppressive activity on both TNBS- and Oxa-induced colitis. The data also provide evidence that glycolipid biosynthesis is involved in the inflammatory cascade in these inflammatory bowel disease (IBD) models.

Topics: 1-Deoxynojirimycin; Adamantane; Animals; Anti-Inflammatory Agents; Antibodies; Body Weight; Colitis; Colon; Disease Models, Animal; Enzyme Inhibitors; Glycolipids; Haptens; Immunoglobulin G; Immunosuppressive Agents; Interferon-gamma; Interleukin-18; Male; Mice; Mice, Inbred C57BL; Oxazolone; Peroxidase; Trinitrobenzenesulfonic Acid

Effects of life-long exposure to high levels of homologous or heterologous growth hormone (GH) and effects of GH resistance on selected parameters of immune function were studied in adult male transgenic mice overexpressing GH releasing hormone (GHRH), bovine (b) GH or an antagonistic bGH analog. In metallothionein I (MT)-bGH transgenic mice with high peripheral levels of bovine GH, there were significant increases in the absolute weight of the thymus and the spleen and in the mitogenic responses of splenocytes to concanavalin A (ConA), lipopolysaccharide (LPS) and phytohemagglutinin (PHA), as compared to age-matched normal animals. There were no significant differences between MT-bGH transgenic and normal mice in splenocyte viability or in delayed-type hypersensitivity measured by the allergic contact dermatitis response to oxazolone. Similar results, including significant stimulation of splenocyte responses to ConA, LPS, and PHA, were obtained in MT-hGHRH transgenic mice in which overexpression of GHRH leads to striking pituitary enlargement and massive elevation of peripheral levels of homologous (mouse) GH. In MT-bGH-antagonist transgenic mice in which overexpression of an antagonistic bGH analog interferes with the actions of endogenous GH, spleen weight was reduced but proliferative responses of splenocytes to ConA, LPS, and PHA were not affected. It is concluded that overexpression of heterologous or homologous GH in transgenic mice can lead to significant stimulation of some parameters of immune function, whereas antagonism of GH action by expression of an antagonistic GH analog does not affect splenocyte responses to mitogens.

Topics: Acromegaly; Animals; Body Weight; Carrier Proteins; Cattle; Cell Division; Cells, Cultured; Gene Expression Regulation; Growth Hormone; Growth Hormone-Releasing Hormone; Hypersensitivity, Delayed; Male; Metallothionein; Mice; Mice, Transgenic; Mitogens; Organ Size; Oxazolone; Promoter Regions, Genetic; Spleen

Offspring of mice treated with cyclophosphamide (Cy; 1, 2.5 or 5 mg/kg) during pregnancy (6-18 days of gestation) and tested for immunocompetence from 5 to 10 weeks of age were found to have defective reticuloendothelial clearance. The main effects were: a) increased elimination half time (T 1/2) of 51Cr-labeled SRBC from circulation, b) decreased liver uptake of 51Cr and c) impaired ability of the spleen, mostly affecting the female pups, to compensate for decreased liver uptake. The highest dose group suffered the most pronounced effects. This group was also found to have increased IgG immunoglobulin levels at 7 weeks of age. IgG antibody production in response to specific antigenic stimulation and delayed hypersensitivity reactions to oxazolone did not appear to be affected by Cy treatment.

Topics: Aging; Animals; Body Weight; Chromium Radioisotopes; Cyclophosphamide; Dermatitis, Contact; Female; Immunocompetence; Immunoglobulin G; Immunoglobulin M; Mice; Mononuclear Phagocyte System; Ovalbumin; Oxazolone; Pregnancy; Prenatal Exposure Delayed Effects; Reticulocytes; Sheep

Acute and delayed hypersensitivity reactions were compared in mice fed diets low in copper (less than 20 mumol copper kg-1) or adequate (more than 300 mumol copper kg-1) for seven to nine weeks after weaning. In the copper depleted animals there was a significant enhancement (P less than 0.01) of histamine-induced paw oedema measured 15 minutes after challenge. The variance of responses within the two dietary groups was similar. Delayed contact hypersensitivity reactions to oxozalone were also significantly increased (P less than 0.01) in the deficient mice. In this study there were some signs of differences in variance heterogeneity but they were statistically insignificant. Delayed-type hypersensitivity to sheep erythrocytes was similarly but less markedly (P less than 0.05) affected. Group differences just failed to reach statistical significance after logarithmic transformation (P less than 0.07) or non-parametric analysis (P less than 0.06). At challenge, the copper deficient mice had a significant (P less than 0.05) plasma hypercholesterolaemia. A few individuals also showed signs of spleen enlargement and mild haemoglobinaemia but otherwise the animals appeared clinically normal and were similar in weight to the controls. Plasma (P less than 0.001), erythrocyte (P less than 0.01) and liver (P less than 0.01) copper concentrations were significantly reduced in the copper-depressed mice, although the concentrations of copper and zinc in the spleen were increased (P less than 0.05) in the same group. Whole blood superoxide dismutase activity was also significantly decreased (P less than 0.01) but erythrocyte glutathione peroxidase activities were similar in both groups, as were blood and liver zinc concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animal Feed; Animals; Body Weight; Copper; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Mice; Mice, Inbred Strains; Organ Size; Oxazolone; Trace Elements