Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma

BACKGROUND: Microbial intestinal colonization in early in life is regarded to play a major role for the maturation of the immune system. Application of non-pathogenic probiotic bacteria during early infancy might protect from allergic disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The aim of the current study was to investigate the immune effects of oral application of probiotic bacteria on allergen-induced sensitization and development of airway inflammation and airway hyper-reactivity, cardinal features of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12) starting from birth for consecutive 8 weeks, during systemic sensitization (six intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all aspects of the asthmatic phenotype: airway reactivity, antigen-specific immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13 cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by mesenteric lymph node cells also showed significant reduction, while TGF production remained unchanged. Oral LGG administration particularly suppressed allergen-induced proliferative responses and was associated with an increase in numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5, 16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic bacteria inhibits subsequent allergic sensitization and airway disease in a murine model of asthma by induction of T regulatory cells associated with increased TGF-beta production.     

Allergy to barium sulfate suspension with angioedema of the stomach and small bowel

Hypersensitivity reactions occurring during barium studies of the gastrointestinal tract are rare. A case is presented with radiographically demonstrated angioedema in the stomach and small bowel accompanied by allergic rhinitis, which was apparently an allergic response to the barium sulfate suspension. The reaction was documented twice during separate challenges to the barium suspension performed several months apart.     

Surgical indications status in ileus using a simple clinical index

Based on a retrospective analysis of a group of patients with ileus disease in regard of the indication for operative intervention an "ileus index" was created which is derived from simple clinical and radiological findings and laboratory data. Prospective evaluation of this index showed its effectiveness in separating patients who had to undergo an emergency operation from those who could be operated electively after preceding diagnostic procedures or could be treated conservatively.     

T-cell costimulatory molecules: optimal targets for the treatment of allergic airway disease with monoclonal antibodies

Current treatment for chronic allergic airway disease with anti-inflammatory agents is effective but not specific, and is symptomatic rather than curative. The present review article outlines the involvement of T cells by dissecting the various steps in which naive CD4+ T cells differentiate to allergen-specific, activated T cells of the TH2 type, which play a pivotal role in the pathogenesis of chronic allergic airway disease. Aiming at a concept for a highly specific therapy of this disease, various T cell costimulatory molecules (CD28, CD27, HVAM, BTLA, ICOS, OX40, CD30, 4-1BB, SLAM, CTLA-4, and PD-1) and the non-costimulatory molecule CD40L, all of them expressed on activated TH2 effector T cells, are discussed as potential targets for an antibody-based therapy. Considering various criteria, including T-cell specific expression and expression characteristics on resting versus activated T cells, reasons are given why ICOS and OX40 can be regarded as optimal targets for such an immunotherapy. Furthermore, arguments are put forward that strongly favor an immunodepletion strategy as compared to an immunoblockade approach, when heading for a specific, long-lasting therapy of chronic allergic airway disease.     

Wilfred Lorenz – The Theoretical Surgeon How it started

Inflammation Research -     

Isolation and characterization of additional genes influencing resistance to various mutagens in the yeast Saccharomyces cerevisiae

Summary Screening of a multi-copy vector-based yeast genomic library in haploid cells of wild-type Saccharomyces cerevisiae yielded transformants hyper-resistant to various chemical mutagens. Genetical analysis of the yeast insert DNAs revealed three genes SNG1, SNQ2, and SNQ3 that confer the phenotype hyper-resistance to MNNG, to 4-NQO and triaziquone, and to mutagens 4-NQO, MNNG, and triaziquone, respectively. Integration of the gene disruption-constructs into the haploid yeast genome yielded viable null-mutants with a mutagen-sensitive phenotype. Thus, copy number of these non-essential yeast genes determines the relative resistance to certain chemical mutagens, with zero copies yielding a phenotype of mutagen sensitivity and multiple copies one of mutagen hyper-resistance, respectively.Dedicated to Professor Dr. R. W. Kaplan on the occasion of his 80th birthday     

Endotoxins prevent murine IgE production,T(H)2 immune responses,and development of airway eosinophilia but not airway hyperreactivity

BACKGROUND: Contact with immunomodulatory factors, such as LPS, in early infancy is associated with decreased allergen sensitization. OBJECTIVE: We sought to study the effects of systemic or airway exposure with LPS on the development of allergen sensitization, eosinophilic airway inflammation, and increased in vivo airway reactivity (AR) in a mouse model. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) plus adjuvant on days 1 and 14 and challenged through the airways with allergen on days 34 to 36. We performed measurement of OVA-specific IgE serum levels, in vitro T(H)2 cytokine production, differential cell counts in bronchoalveolar lavage fluids, and assessment of in vivo AR to inhaled methacholine by means of barometric whole-body plethysmography. RESULTS: Systemic LPS administration before OVA sensitization reduced OVA-specific IgE serum levels (426 +/- 76 vs 880 +/- 104 U/mL, P <.01), T(H)2 cytokine production by splenic mononuclear cells (IL-4: 0.08 +/- 0.01 vs 0.17 +/- 0.01 ng/mL; IL-5: 1.98 +/- 0.52 vs 4.11 +/- 0.54 ng/mL; P <.01), and extent of airway eosinophilia (total cell counts: 93 vs 376 x 10(3)/mL; eosinophils: 23% vs 51%; P <.01) compared with that in OVA-sensitized mice. Local LPS administration to sensitized mice before airway allergen challenges particularly induced IFN-gamma production by peribronchial lymph node cells in vitro (1718 +/- 315 vs 483 +/- 103 ng/mL, P <.01) associated with reduced airway eosinophilia compared with that seen in OVA-sensitized mice. Development of increased AR was not affected by systemic or local LPS exposure. Inhibitory effects of LPS on allergen sensitization and eosinophilic airway inflammation were inhibited by administration of anti-IL-12 antibodies before LPS exposure. CONCLUSION: These data indicate that local and systemic application of LPS modulates systemic and local T(H)1/T(H)2 immune responses in a distinct but similarly IL-12-dependent mode.