interleukin-8 and perflubron

Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and alpha-toxin. We hypothesised that the perfluorocarbons (PFCs), perflubron and FC-84, would block stimulation of A549 cells by these toxins.. The levels of IL-8 production in A549 cells were measured following exposure to toxins for 24 h with or without PFC. The amount of IL-8 released from A549 cells was measured by enzyme-linked immunosorbent assay, and the level of IL-8 mRNA was measured by real-time RT-PCR.. When stimulated with LPS or alpha-toxin, IL-8 release from A549 cells increased. There were no significant differences in level of IL-8 release between cells pre-incubated for 24 h with or without PFC after toxin stimulation for 24 h. When PFC was administered along with LPS stimulation, the level of IL-8 release was decreased (LPS control, 1,398 +/- 110 pg/well; FC-84, 686 +/- 50 pg/well; perflubron, 749 +/- 137 pg/well; p < 0.05). Levels of IL-8 mRNA expression were significantly higher with than without LPS, and those with LPS and perflubron were significantly lower than those with LPS alone.. The results show that PFCs block stimulation of A549 cells by LPS or alpha-toxin. PFC may be useful clinically in treatment of pulmonary inflammation in the alveolar space.

Topics: Blood Substitutes; Cells, Cultured; Dose-Response Relationship, Drug; Drug Combinations; Fluorocarbons; Humans; Hydrocarbons, Brominated; Interleukin-8; Lipopolysaccharides; Pulmonary Alveoli; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Type C Phospholipases

To determine the protective effect of perflubron (PFB), a type of perfluorochemical liquid, in hyperoxia-induced cellular injury in the human airway epithelial cells.. A controlled, in vitro laboratory study.. Tertiary-care children's hospital.. Human airway epithelial cells.. Human airway epithelial cells, Calu-3 cells, grown on polycarbonate porous filters at an air-liquid interface culture were exposed to normoxic (Fico(2) = 5%, balance air) or hyperoxic (Fio(2) = 95%, balance CO(2)) conditions. Hyperoxia-induced cellular changes were monitored by measuring transepithelial resistance (TER) of monolayers, histology of cells, total protein, and interleukin-8 (IL-8) secretion in apical surface fluid (ASF) washings. Under hyperoxic conditions, the protective effect of PFB was assessed by directly adding PFB liquid to the apical surface of monolayers.. During hyperoxic gas-liquid interface culture, Calu-3 monolayers exhibited a loss of cellular integrity morphologically, decreased protein concentration, and IL-8 level in ASF washings. During hyperoxic PFB-liquid interface culture, there was an overall increase in TER value of monolayers, improved histology, decreased total protein secretion in ASF washings, and unaltered IL-8 secretion. Cytomorphologic observations of PFB-treated Calu-3 cells indicated the presence of varying numbers of differently sized intracellular vacuoles during both normoxic and hyperoxic conditions.. We conclude that the air-liquid interface culture of Calu-3 may be helpful in understanding mechanisms of lung injuries caused in clinical practice, and PFB protects against hyperoxia-induced airway epithelial cell injury by promoting cellular integrity as well as cytologic modifications. PFB-liquid interface culture of Calu-3 may be a useful in vitro model for studying the cytoprotective role of liquid ventilation.

Topics: Cell Culture Techniques; Epithelial Cells; Fluorocarbons; Humans; Hydrocarbons, Brominated; Hyperoxia; Interleukin-8; Liquid Ventilation; Lung; Respiratory Insufficiency

The study investigates the effectiveness of aerosol treatment on gas exchange and pulmonary inflammatory reaction using perfluorocarbons with different molecular structure and vapor pressure.. Experimental, prospective, randomized, controlled study.. Experimental laboratory at a university hospital.. Twenty anesthetized neonatal piglets assigned to four groups.. After establishment of lung injury by bronchoalveolar lavage, piglets either received aerosolized FC77 (n = 5), perfluorooctylbromide (n = 5), or FC43 (n = 5, 10 mL x kg(-1) x hr(-1) for 2 hrs) or intermittent mandatory ventilation (control, n = 5). Thereafter, animals were supported for another 6 hrs.. Pao2 significantly improved in the perfluorocarbon groups compared with control (p < .01). Final Pao2 (mean +/- SEM) was FC77, 406 +/- 27 mm Hg; perfluorooctylbromide, 332 +/- 32 mm Hg; FC43, 406 +/- 19 mm Hg; control, 68 +/- 8 mm Hg. Paco2 and mean pulmonary arterial pressure were lower in all perfluorocarbon groups compared with control. The ratio of terminal dynamic compliance to total compliance was significantly higher in the FC77 than in the FC43, perfluorooctylbromide, and control groups. Relative gene expression of interleukin-1beta, interleukin-8, P-selectin, E-selectin, and intercellular adhesion molecule-1 in lung tissue was determined by TaqMan real time polymerase chain reaction normalized to hypoxanthineguanine-phosphoribosyl-transferase and was shown to be reduced by all perfluorocarbons.. Aerosol treatment with all the perfluorocarbons investigated improved gas exchange and reduced pulmonary inflammatory reaction independently from molecular structure and vapor pressure of the perfluorocarbons. Although differences in vapor pressure and molecular structure may account for varying optimal dosing strategies, several different perfluorocarbons were shown to be principally suitable for aerosol treatment.

Topics: Administration, Inhalation; Aerosols; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; E-Selectin; Fluorocarbons; Gene Expression; Humans; Hydrocarbons, Brominated; Infant, Newborn; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Liquid Ventilation; Lung Compliance; Molecular Structure; P-Selectin; Pulmonary Gas Exchange; Pulmonary Surfactants; Pulmonary Wedge Pressure; Random Allocation; Respiratory Distress Syndrome, Newborn; Swine