ovalbumin and Liver-Cirrhosis

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Topics: Adjuvants, Immunologic; Animals; Animals, Newborn; Animals, Suckling; Antibodies, Helminth; CD4-Positive T-Lymphocytes; Cercaria; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Forkhead Transcription Factors; Granuloma, Foreign-Body; Immunity, Heterologous; Immunity, Humoral; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-4; Liver Cirrhosis; Liver Diseases, Parasitic; Male; Mice; Mothers; Ovalbumin; Pregnancy; Schistosoma mansoni; Schistosomiasis mansoni; Spleen

CD1d-restricted natural killer T (NKT) cells are implicated in the pathogenesis of asthma. β-Glucosylceramide (GC), a naturally occurring lipid, was previously shown to alter NKT cell distribution in the liver. We hypothesized that GC can affect lung and liver NKT cell distribution and ameliorate asthma. Mice were sensitized by intra-peritoneal injection of ovalbumin (OVA) for 2 weeks followed by repeated intranasal OVA challenges to induce lung injury mimicking asthma. OVA induced asthma groups were either treated by intranasal instillation of normal saline, intranasal instillation of GC or inhaled budesonide. To investigate the role of the liver, hepatic fibrosis was induced using carbon tetrachloride prior to asthma induction. Allergen induced bronchoconstriction was measured prior to sacrifice. Isolated lymphocytes from lungs, livers and spleens were analyzed for OVA induced proliferation and flow cytometry. Liver and lung histology, serum aminotransferase and anti-OVA antibodies level were assessed. Treatment with GC significantly reduced OVA induced airway responsiveness (p<0.001) similar to inhaled budesonide. GC significantly reduced the peri-bronchial and peri-vascular inflammatory infiltration mainly through an effect on T cells, as suggested by decreased T cell proliferation (p=0.009). Liver CD4 and NKT cells significantly increased after GC treatment suggesting liver involvement. Inducing hepatic fibrosis blunted the propagation of asthma in spite of sufficient increase of serum anti-OVA titers. GC has an immunomodulatory effect on a murine model of experimental asthma. We also suggest that the liver acts as an immunomodulatory organ and might have a regulatory effect on pulmonary diseases.

Topics: Allergens; Animals; Asthma; Carbon Tetrachloride; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Glucosylceramides; Immunomodulation; Liver; Liver Cirrhosis; Lung; Lymphocyte Activation; Mice; Natural Killer T-Cells; Ovalbumin

When normal individuals eat 0.33 g protein N/kg body weight (BW)((3/4)) per day, they excrete 10-15 mg urea N/h per kg BW((3/4)). If they now ingest (at 0 h) 0.27 (dose A), 0.40 (dose B), 0.53 (dose C), 0.94 (dose D), or 1.33 (dose E) g protein N/kg BW((3/4)) (in the form of casein, ovalbumin, or lactalbumin), the rate of urea N excretion accelerates within 4 h. At dose C a maximal rate of urinary urea N excretion (MRUE) is reached, which averages 55 mg urea N/h per kg BW((3/4)) and which persists for 16 h. Higher doses of protein do not further accelerate urea excretion, but prolong the duration of MRUE to 28 h (after dose E). Blood urea N (BUN) rises by 7-20 mg/100 ml during the first 8 h after dose C to E, and remains stable within +/-5 mg/100 ml during the ensuing 8-28 h of MRUE. Each increment of protein above dose C causes a further increment in plasma alpha-amino N. During infusion of free amino acids at a rate of 110 or 165 mg amino acid N/h per kg BW((3/4)) for 12 h, rate of urea excretion increases to the MRUE value produced by dose C-E of oral protein.These findings indicate that MRUE corresponds to a period of maximal rate of urea synthesis (MRUS). MRUS is greater than MRUE because one fraction of newly formed urea is hydrolyzed in the gastrointestinal tract, and another fraction may accumulate temporarily in body water during the MRUE period. Oral neomycin reduces the proportion of urea hydrolyzed in the gut to less than 20%; its extent is measured by recovery in the urine of a tracer dose of [(14)C]urea injected intramuscularly during determination of MRUE. Accumulation of urea in body water is estimated from increment in BUN during the period of MRUE measurement (8-24 h after dose E of casein) and from body water measured with (3)H(2)O. Then MRUS is calculated as: ([mg urea N excreted between 8 and 24 h after dose E] + [BUN at 24 h - BUN at 8 h] x [body water]) x (100/% recovery [(14)C]urea) x (1/kg BW((3/4))) x (1/16 h).MRUS in 10 normal subjects averaged 65 mg urea N/h per kg BW((3/4)) (range 55-76), and in 34 cirrhotics 27 mg urea N/h per kg BW((3/4)) (range 6-64). Among 19 cirrhotic patients fed 40, 60, 80, or 100 g protein daily for successive 10 day periods, the occurrences of hyperammonemia, hyperaminoacidemia, and encephalopathy at each level of protein intake were inversely related to MRUS value.

Topics: Administration, Oral; Amino Acids; Ammonia; Ammonium Chloride; Bilirubin; Body Surface Area; Body Water; Body Weight; Carbon Isotopes; Caseins; Creatinine; Electroencephalography; Hemoglobins; Humans; Injections, Intravenous; Lactalbumin; Liver Cirrhosis; Neomycin; Ovalbumin; Portacaval Shunt, Surgical; Tritium; Urea