ABSTRACT
Tumor necrosis factor-alpha (TNF) is implicated as an important proinflammatory cytokine in asthma. We evaluated mice deficient in TNF receptor 1 (TNFR1) and TNFR2 [TNFR(-/-) mice] in a murine model of allergic inflammation and found that TNFR(-/-) mice had comparable or accentuated responses compared with wild-type [TNFR(+/+)] mice. The responses were consistent among multiple end points. Airway responsiveness after methacholine challenge and bronchoalveolar lavage (BAL) fluid leukocyte and eosinophil numbers in TNFR(-/-) mice were equivalent or greater than those observed in TNFR(+/+) mice. Likewise, serum and BAL fluid IgE; lung interleukin (IL)-2, IL-4, and IL-5 levels; and lung histological lesion scores were comparable or greater in TNFR(-/-) mice compared with those in TNFR(+/+) mice. TNFR(+/+) mice chronically treated with anti-murine TNF antibody had BAL fluid leukocyte numbers and lung lesion scores comparable to control antibody-treated mice. These results suggest that, by itself, TNF does not have a critical proinflammatory role in the development of allergic inflammation in this mouse model and that the production of other cytokines associated with allergic disease may compensate for the loss of TNF bioactivity in the TNFR(-/-) mouse.
Subject(s)
Asthma/immunology , Pneumonia/immunology , Receptors, Tumor Necrosis Factor/genetics , Receptors, Tumor Necrosis Factor/immunology , Aerosols , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Immunoglobulin E/blood , Immunoglobulin G/blood , Interferon-gamma/analysis , Interleukin-2/analysis , Interleukin-4/analysis , Interleukin-5/analysis , Mice , Mice, Inbred C57BL , Mice, Knockout , Ovalbumin/immunology , Ovalbumin/pharmacology , Respiratory Hypersensitivity/immunology , Signal Transduction/immunology , T-Lymphocyte Subsets/immunology , Tumor Necrosis Factor-alpha/analysisSubject(s)
Bone Resorption/urine , Collagen/urine , Peptides/urine , Biomarkers/urine , Collagen Type I , Humans , Immunoassay/instrumentation , MiniaturizationABSTRACT
STUDY OBJECTIVES: With renewed interest in intraosseous (IO) infusion, the present study examined if sternal IO infusion provided vascular entry of 7.5% NaCl/6% dextran-70 (HSD) as efficiently as IV infusion. DESIGN, SETTING, TYPE OF PARTICIPANTS, INTERVENTIONS: Twelve anesthetized pigs were catheterized for measurement of cardiovascular parameters. Six pigs were given a 4-mL/kg IO infusion of HSD under pressure over two to six minutes; each pig was paired with another that had been given HSD IV over the same time course. Rapid arterial blood sampling was used to evaluate vascular entry of NaCl and dextran with monitoring continued for two hours after infusion. MEASUREMENTS AND MAIN RESULTS: Complete vascular entry of infused sodium and dextran was generally complete within one minute after infusion in all experiments. Increases in mean arterial pressure, cardiac output, and other cardiovascular parameters were indistinguishable between IO and IV infusions. Plasma volume expansion was about 20% above baseline in both groups of pigs. Histologic examination showed minimum pathology to the sternum and no significant pulmonary complications. CONCLUSION: 1O vascular delivery of HSD is a viable alternative in emergency scenarios in which vascular access is compromised.
