Aminophylline-induced suppression of pulmonary antibacterial defenses. 1985

S Nelson, and W R Summer, and G J Jakab

Respiratory infections are frequently observed in patients with chronic obstructive pulmonary disease, indicating that host defenses are compromised. Antibacterial defenses of the lung against such infections include the alveolar macrophage and polymorphonuclear leukocytes (PMN) that migrate into the lung to provide auxiliary phagocytic defenses. To test the hypothesis that aminophylline acutely impairs pulmonary antibacterial defenses, mice were challenged by aerosol inhalation with Staphylococcus aureus or Proteus mirabilis and injected intraperitoneally with aminophylline (20, 40, or 80 mg/kg). Pulmonary bactericidal activity and total lavaged lung cell and differential counts were determined 4 h after bacterial challenge. The highest dose of aminophylline suppressed the killing of S. aureus so that 55 +/- 5% of the initial viable bacteria remained as compared with 22 +/- 4% in the control animals. In contrast, there was a dose-related suppression of pulmonary antibacterial defenses against gram-negative bacteria. With doses of 40 and 80 mg/kg, lung defenses were ablated, allowing the proliferation of P. mirabilis to 115 +/- 9% and 253 +/- 9%, respectively, the control value being 26 +/- 3%. The number of PMN obtained by lavage after aerosol challenge with P. mirabilis was also inhibited by aminophylline in a dose-dependent manner. From the lungs of untreated animals 5.0 +/- 0.3 X 10(6) PMN were recovered as compared with 3.3 +/- 0.1 X 10(6), 2.5 +/- 0.2 X 10(6), and 1.8 +/- 0.1 X 10(6), respectively, with increasing doses of aminophylline. The bactericidal activity of lavaged PMN from the lungs of aminophylline-treated rats challenged with the gram-negative bacterium in vivo was significantly depressed when compared with that in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007165 Immunosuppression Therapy Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. Antirejection Therapy,Immunosuppression,Immunosuppressive Therapy,Anti-Rejection Therapy,Therapy, Anti-Rejection,Therapy, Antirejection,Anti Rejection Therapy,Anti-Rejection Therapies,Antirejection Therapies,Immunosuppression Therapies,Immunosuppressions,Immunosuppressive Therapies,Therapies, Immunosuppression,Therapies, Immunosuppressive,Therapy, Immunosuppression,Therapy, Immunosuppressive
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011512 Proteus Infections Infections with bacteria of the genus PROTEUS. Infections, Proteus,Infection, Proteus,Proteus Infection
D011513 Proteus mirabilis A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is frequently isolated from clinical specimens. Its most common site of infection is the urinary tract.
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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