Mycoplasma pneumoniae Induces Chronic Respiratory Infection, Airway Hyperreactivity, and Pulmonary Inflammation: a Murine Model of Infection-Associated Chronic Reactive Airway Disease

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r = -0.95, P = 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P = 0.03) and increased airway obstruction at 530 days (P = 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.     

Effect of clarithromycin on cytokines and chemokines in children with an acute exacerbation of recurrent wheezing: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity. OBJECTIVE: To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing. METHODS: Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind, randomized trial of clarithromycin vs placebo. Concentrations of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, RANTES, eotaxin, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, and monocyte chemoattractant protein 1 were measured in serum and/or nasopharyngeal aspirates before, during, and after therapy. Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing. RESULTS: Nasopharyngeal concentrations of TNF-alpha, IL-1beta, and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo. There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection. No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo. CONCLUSION: Clarithromycin therapy reduces mucosal TNF-alpha, IL-1beta, and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing.     

Studies with a pathogenic and an attenuated strain of Venezuelan equine encephalitis virus and aedes aegypti (L.) mosquitoes

Summary Venezuelan equine encephalitis virus was passaged in KB cell cultures. The virus lost its mouse pathogenicity following subcutaneous inoculation during KB cell passage; the attenuated strain also produced smaller plaques than the pathogenic strain. Both strains grew to the same extent inAedes aegypti (L.) mosquitoes after intrathoracic inoculation. If any reversions to pathogenicity occur during development of the attenuated virus in mosquitoes, then the mutation frequency per duplication per particle must be smaller than 3.5×10^–6.     

Correction to: Longitudinal associations of physical fitness and affect with depression,anxiety and life satisfaction in adult women with fibromyalgia

Quality of Life Research -     

p,p′-DDE,a DDT metabolite,induces proinflammatory molecules in human peripheral blood mononuclear cells “in vitro”

In a recent study, our group demonstrated that when peripheral blood mononuclear cells (PBMCs) were treated “in vitro” with p,p′-DDE, a DDT metabolite, an antioxidant response and biomarkers of inflammation were induced at the mRNA level, indicating a proinflammatory state. Thus, the aim of this study was to evaluate the induction of proinflammatory molecules at the protein level in PBMCs exposed to p,p′-DDE “in vitro”. The main finding was that “in vitro” exposure to p,p′-DDE enhanced the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6) at the protein level in PBMCs. We also observed COX-2 induction at the protein level. Considering that p,p′-DDE has been identified as a persistent metabolite and is frequently found in the population, it is important to evaluate early inflammation biomarkers in populations exposed to DDT and to estimate the true risk of inflammatory disease development.     

Comparative scanning electron microscopy of bullous diseases

The purpose of this study is to compare scanning electron microscopy findings of the blister roof in three distinct bullous diseases: one intraepidermal acantholytic (pemphigus foliaceus); one due to hemidesmosomal dysfunction (bullous pemphigoid); and one secondary to anchoring fibril dysfunction - type VII collagen (dystrophic epidermolysis bullosa). In pemphigus foliaceus, acantholytic phenomena were readily demonstrated. In bullous pemphigoid, the epidermis had a solid aspect. In dystrophic epidermolysis bullosa a net was seen in the blister roof.     

Respiratory syncytial virus pneumonia: mechanisms of inflammation and prolonged airway hyperresponsiveness

PURPOSE OF REVIEW: Respiratory syncytial virus is the leading viral pathogen associated with lower respiratory tract infection in young children worldwide. The pathogenesis of acute bronchiolitis and the mechanisms by which the virus induces long-term airway disease remain to be elucidated. This review highlights new findings reported in the English-language medical literature from January 2004 to January 2005. RECENT FINDINGS: Several studies have confirmed a strong association between respiratory syncytial virus infection in infancy and an increased risk for recurrent wheezing. Evidence indicates that the exaggerated immune response and abnormal neurogenic mechanisms induced by the virus play a significant role in the pathogenesis of the disease. Different genetic and immune markers have been correlated with acute disease severity and with increased risk of long-term pulmonary abnormalities. Recently, the application of real time polymerase chain reaction has demonstrated the persistence of respiratory syncytial virus RNA in the lungs of infected mice for months after inoculation. This unexpected observation has stimulated discussions as to whether the long-term presence of the virus could contribute to the long-term airway disease observed in children after respiratory syncytial virus lower respiratory tract infection. SUMMARY: Despite almost half a century of active research into the pathogenesis of respiratory syncytial virus-induced acute and chronic airway disease, many questions remain unresolved. Studies in animal models demonstrate that interventions reducing viral replication resulted in improvement of acute disease severity and long-term pulmonary abnormalities. The stage is ready for clinical studies to determine whether preventing or delaying the primary infection could reduce the incidence of recurrent wheezing in children.