Biomedical subjects

Heinz-Gerd Hoymann

Publications and source records attributed to Heinz-Gerd Hoymann.

3 recordsLinked to original sources

PubMed2006

New developments in lung function measurements in rodents.

There are invasive and noninvasive pulmonary function tests available which are sensitive in detecting bronchoconstriction in rodents. Noninvasively measured midexpiratory flow (EF50) has been shown to be an appropriate parameter to monitor bronchoconstriction in a large number of animals, e.g. for screening purposes. Recently, a novel technique for repetitive lung function measurements in orotracheally intubated, spontaneously breathing mice has been established. Bronchoconstriction is assessed by the "gold standard" parameters airway resistance and dynamic compliance in response to aerosolized methacholine or allergens in anesthetized mice. This measurement technique has been combined with an inhalation technique which has been optimized to allow simultaneous lung function measurement in intubated animals and to obtain high aerosol concentrations. A feedback dose control system has been developed to administer a defined and constant aerosol dose to each individual animal. Using this system a prominent early allergic response and late airway hyperresponsiveness could be demonstrated in intubated mice challenged with Aspergillus fumigatus allergen. We conclude: The noninvasive EF50 method seems particularly appropriate for measurements of respiratory function in large numbers of conscious mice in assembly line fashion. The invasive technology--newly established for the mouse--is more sensitive and specific since true airway resistance and dynamic compliance are determined and allows now the adequate detection of an early allergic response in the mouse and also repetitive measurements e.g. to assess the airway hyperresponsiveness in the same animal or for monitoring purposes in chronic models.

Animals↗

PubMed2006

CD137-mediated immunotherapy for allergic asthma.

The prevalence of asthma continues to increase. Asthma is caused by a Th2 cell-driven immune response. Its optimal treatment remains a challenge, and a sufficient immunotherapeutic approach to treating asthma has yet to be found. Using a murine asthma model, we show that a single injection of an anti-CD137 (4-1BB) mAb prevents the development of airway hyperreactivity, eosinophilic airway inflammation, excessive mucus production, and elevated IgE during the observation period of 7 weeks. Most importantly, even established disease is completely reversed by anti-CD137 mAb administration. The protection is associated with markedly reduced Th2 cytokine production and increased secretion of the Th1 cytokine IFN-gamma. While B lymphocytes are partly depleted, the number of CD8+ T cells is increased. Blockade of IFN-gamma and depletion of CD8+ T cells during treatment with anti-CD137 mAb reduces in part but does not abrogate the protective effect of CD137 mAb. In contrast, CD137 mAb-mediated CD4+ T cell anergy is critical for the observed effects, since transfer of CD4+ T cells from CD137 mAb-treated mice conveyed protection. These data demonstrate, for the first time to our knowledge, the capacity of anti-CD137 mAb to ameliorate allergic asthma, and they indicate CD137 as a possible target for therapeutic intervention in this disease.

Animals↗

PubMed2005

Blocking IL-15 prevents the induction of allergen-specific T cells and allergic inflammation in vivo.

IL-15 has been shown to accelerate and boost allergic sensitization in mice. Using a murine model of allergic sensitization to OVA, we present evidence that blocking endogenous IL-15 during the sensitization phase using a soluble IL-15Ralpha (sIL-15Ralpha) suppresses the induction of Ag-specific, Th2-differentiated T cells. This significantly reduces the production of OVA-specific IgE and IgG and prevents the induction of a pulmonary inflammation. Release of proinflammatory TNF-alpha, IL-1beta, IL-6, and IL-12 as well as that of Th2 cytokines IL-4, IL-5, and IL-13 into the bronchi are significantly reduced, resulting in suppressed recruitment of eosinophils and lymphocytes after allergen challenge. It is of clinical relevance that the airway hyper-responsiveness, a major symptom of human asthma bronchiale, is significantly reduced by sIL-15Ralpha treatment. Ex vivo analysis of the draining lymph nodes revealed reduced numbers of CD8, but not CD4, memory cells and the inability of T cells of sIL-15Ralpha-treated mice to proliferate and to produce Th2 cytokines after in vitro OVA restimulation. This phenomenon is not mediated by enhanced numbers of CD4(+)/CD25(+) T cells. These results show that IL-15 is important for the induction of allergen-specific, Th2-differentiated T cells and induction of allergic inflammation in vivo.

Allergens↗