Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the potentials and limitations of various animal models of sepsis are discussed to clarify to which extent these findings are relevant to human sepsis. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models using different animal species including rats, mice, rabbits, dogs, pigs, sheep, and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be replaced by other methods. New therapeutic agents should be studied in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 µg of DEP/10 µl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.

To evaluate the effects of a heat and moisture exchanger and a heated humidifier on respiratory mucus and transportability by cilia and cough in patients undergoing invasive mechanical ventilation (up to 72 hrs). Prospective, randomized, clinical study. General intensive care unit and university research laboratory. A total of 32 consecutive patients with acute respiratory failure, who were intubated and mechanically ventilated in the intensive care unit setting, were enrolled in the study. Patients were randomly assigned to receive as a humidifying system a heat and moisture exchanger (HME) or heated humidified water (HHW) at the onset of mechanical ventilation (time 0). Respiratory mucus samples were collected by suction using a sterile technique at time 0, 24, 48, and 72 hrs of mechanical ventilation. Eleven patients were excluded from this study because of either extubation or death before 72 hrs of mechanical ventilation, leaving 12 patients in the HME group and nine patients in the HHW group. Ventilatory variables including minute volume, mean airway pressure, positive end-expiratory pressure, Fio2, as well as Pao2/Fio2 ratio, fluid balance (last 6 hrs), furosemide, and inotrope administration (last 4 hrs) were recorded. In vitro mucus transportability by cilia was evaluated on the mucus-depleted frog palate model, and the results were expressed as the mucus transport rate. Cough clearance (an estimation of the interaction between the flow of air and the mucus lining the bronchial walls) was measured using a simulated cough machine, the results being expressed in millimeters. Mucus wettability was measured by the contact angle between a mucus sample drop and a flat glass surface. Mucus rheologic properties (mechanical impedance [log G*] and the ratio between viscosity and elasticity [tan delta]) were measured using a magnetic microrheometer at 1 and 100 cGy/sec deformation frequency. The two humidification groups were comparable in terms of the Acute Physiology and Chronic Health Evaluation II score, age, gender, ventilatory variables, fluid balance, use of inotropes, and furosemide. Ours results indicate that air humidification with either HME or HHW at 32 degrees C (89.6 degrees F) has similar effects on mucus rheologic properties, contact angle, and transportability by cilia in patients undergoing mechanical ventilation, except for transportability by cough, which diminished after 72 hrs of mechanical ventilation in the HME group (p = .0441).