lipid-a and Acute-Disease

Topics: Acute Disease; Anti-Bacterial Agents; Chemical Phenomena; Chemistry; Complement Activation; Endotoxins; Humans; Lipid A; Lipopolysaccharides; Respiratory Insufficiency; Salmonella typhimurium

The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37. Blood samples were collected from the retro-orbital sinus, on days 0, 23, and 40. The serum levels of IL-4, IFN-γ, IgE, and IgG2a were measured using ELISA technique. The blood number of Th1 and Treg cells was determined using flow cytometry. At the sensitization phase, the number of Th1 and the serum levels of IFN-γ and IgG2a were significantly increased in the Derp2-sensitized group pretreated with CPG plus MPLA, and the number of Treg cells was significantly elevated in Derp2-sensitized mice pretreated with CPG or CPG plus MPLA as compared with that in Derp2-sensitized control mice. At the challenge phase, the number of Th1 was significantly elevated in Derp2-sensitized mice pretreated with CPG plus MPLA, CPG plus BCG, or CPG; the count of Treg cells was significantly increased in Derp2-sensitized mice pretreated with CPG plus BCG group; and the levels of IFN-γ and IgG2a were significantly enhanced in the Derp2-sensitized group pretreated with CPG plus MPLA in comparison with those in Derp2-sensitized control mice. The scores of inflammation and mucus secretion in the lung were significantly decreased in the Derp2-sensitized group pretreated with CPG, BCG, and CPG plus MPLA in comparison with those in the Derp2-sensitized control group. These results showed that BCG, MPLA, and CPG modulate Th1-, Th2-, and Treg-related parameters and ameliorate lung inflammatory parameters in a mouse model of asthma.

Topics: Acute Disease; Adjuvants, Immunologic; Animals; Antigens, Dermatophagoides; Asthma; Immunomodulation; Inflammation; Lipid A; Mice; Mice, Inbred BALB C; Mycobacterium bovis; Oligodeoxyribonucleotides; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells

We studied the role of adhesion molecules in acute lung injury caused by lipopolysaccharide (LPS). Forty-eight female guinea pigs were divided into three groups: saline (n = 12); B464, an LPS antagonist, (0.2 mg/kg i.v.) (n = 12); LPS (0.02 mg/kg i.v.) (n = 12); and LPS + B464 (n = 12). The numbers of polymorphonuclear cells (PMN) in blood sampled over 4 hours were counted. Accumulation of PMNs in the lungs was determined by counting the number of PMNs in lung-tissue samples fixed for light-microscopic examination. The lung wet-to-dry weight ratio and the 125I-albumin tissue-to-plasma ratio were used to assess lung injury. Human umbilical-vein endothelial cells were treated with B464 and then stimulated with either LPS or tumor necrosis factor. Expression of ICAM-1 and ELAM-1 was estimated by enzyme-linked immunosorbent assay. After LPS injection, light microscopy revealed decreases in peripheral PMN counts, and accumulation of PMNs in the lungs. Increases in the two indices of lung injury were also observed. These changes were attenuated by prior treatment with B464. The LPS-induced increases in ICAM-1 and ELAM-1 expression were dose-dependently suppressed by B464. These results suggest that pulmonary accumulation of activated PMNs plays an important role in LPS-induced lung injury.

Topics: Acute Disease; Animals; Cells, Cultured; Disease Models, Animal; E-Selectin; Endothelium, Vascular; Female; Guinea Pigs; Humans; Intercellular Adhesion Molecule-1; Lipid A; Lipopolysaccharides; Lung Diseases

Topics: Acute Disease; Antibodies, Bacterial; Antigens, Bacterial; Antigens, Surface; Cell Wall; Chronic Disease; Enterobacteriaceae; Female; Humans; Immunity, Cellular; Lipid A; Male; O Antigens; Pyelonephritis; Virulence