Augmentation of allergic early-phase reaction by nerve growth factor

The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is caused by allergen and immunoglobulin E-dependent mediator release from mast cells. It was previously shown that nerve growth factor (NGF) contributes to acute airway inflammation. This study further investigates the role of NGF in the allergic early-phase reaction using a well-established mouse model of ovalbumin-induced allergic airway inflammation. Treatment of sensitized and aerosol challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen-induced early-phase reaction and suppressed airway inflammation. Transgenic mice constitutively overexpressing NGF in the airways (Clara-cell secretory protein promoter [CCSP]-NGF-tg) were employed and compared with wild-type animals. In sensitized and challenged CCSP-NGF-tg mice, early-phase reaction, airway inflammation, as well as percental relative increases in serotonin levels were augmented compared with wild-type mice. These effects were paralleled by increased serotonin levels in the airways, whereas immunoglobulin E levels remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF-mediated neuronal plasticity. These data provide evidence for the functional role of NGF in the development of allergic early phase responses in the airways and the lung.     

Rheumatoid arthritis: scientific development from a critical point of view

Rheumatoid arthritis (RA) is classified as a chronic, progressive, systemic autoimmune disorder leading to inflammation, stiffness, defective position and destruction of joints. Finally a complete loss of mobility and functioning can be the result. The fraction of disability varies strongly, for example, a systematic review shows a 50% disability in a period from first occurrence to disability from 4.5 to 22 years. Scientific efforts focused strongly on therapeutic and diagnostic methods during recent years. So far, there is no scientometric approach of the topic rheumatoid arthritis available although there is an increased need to evaluate quality and quantity of scientific research. Density-equalizing algorithms, scientometric methods and large scale data analysis were applied to evaluate the quality and quantity of scientific efforts in the field of rheumatoid arthritis. Data were gained from Pubmed and ISI-Web. During the period 1901–2007, 78,128 items were published by 129 countries including the USA, UK and Germany being the most productive suppliers, representing 45.7% of all publications. Another 23 countries published more than 100 items. In terms of international cooperation the USA proved to be the most successful partner. “Arthritis and Rheumatism”, “Annals of the Rheumatic Diseases” and the “Journal of Rheumatology” are the most prolific journals. The current study is the first analysis of “rheumatoid arthritis” research activities and output. Our analysis revealed single areas of interest, the most prolific journals, authors and institutions dealing with the topic. Nevertheless, statements concerning the scientific quality should be considered critical due to a bias according to self-citation and co-authorship.     

Cruciate ligament injuries under gender aspects

An injury of cruciate ligament is one the most common knee injuries. This accident happens mostly without external impact and towards the end of training and competition sessions. Women, especially athletes playing team sports ball games such as soccer or disciplines such as tennis, are affected 2 to 8 times more often than men. Anatomic, biomechanical and endocrinological differences are currently discussed as potential risk factors. In terms of prevention, biomechanical impact is of greatest importance given its influenceability through various training opportunities. Training programs including endurance aspects, strengthening knee musculature, balance as well as plyometric trainings were most effective. Further studies should focus more on concomitants of course of injuries.     

Arbeitsunfall im professionellen B��hnentanz

One in two professional dancers sustains an acute injury in an occupational accident during the course of an annual work period. Nevertheless, in a medical surgery it is usually extremely rare to be confronted with an occupational accident of a professional dancer. The primary treatment is ?C similar to other occupations ?C decisive for the rehabilitation, though. Basic knowledge of the work-specific distress and a basic dancers?? vocabulary are beneficial. In addition to that, basic knowledge of the English language is required as German is a foreign language for the majority of professional dancers.     

Immunglobulin concentrations in cerebrospinal fluid of children. Studies regarding age dependency and changes during inflammatory disease of CNS (author's transl)

75 children of different age groups were examined for immunglobulin concentrations in spinal fluid. No statistical significant differences were found between the age groups a) 1 month to 1 year, b) 1 year to 5 years and c) 5 years to 12 years. The average level for IgG was 1,41 +/- 0,8 mg%, for total protein 34,8 +/- 9,6 mg%. IgA and IgM were detectable not or only in small quantities even when the spinal fluid was concentrated. Furthermore 21 children with viral and 9 with purulent meningitis and 2 with encephalitis were examined. Patients with meningitis had a distinct increase in IgG, IgA and IgM. The increase was more pronounced in purulent than in viral meningitis. Children with encephalitis had an increase of IgG and in one case an increase of IgA. Continous examination of immunglobulins in spinal fluid from a child with inoperable hydrocephalus revealed a steady increase of all 3 immunglobulins which was probably a result of elevated vascular permeability.     

Tumor necrosis factor-alpha and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes

Activated macrophages have been shown to produce brain-derived neurotrophic factor (BDNF) in diseases such as multiple sclerosis (MS) or allergic bronchial asthma (BA). However, there is little data on BDNF regulation in these cells. We demonstrate that unstimulated human peripheral blood monocytes, but not lymphocytes, constitutively secrete BDNF. IL-6 and TNF-alpha specifically enhanced BDNF secretion in monocytes, whereas typical Th1- and Th2-cytokines did not show any effect. None of the cytokines induced BDNF secretion in T- or B-cells. Thus, our data provide evidence that IL-6 and TNF-alpha represent a specific link between monocyte infiltration and neuronal changes in inflammatory diseases.     

CD8(+) T cells regulate immune responses in a murine model of allergen-induced sensitization and airway inflammation

The role of CD8(+) T cells in the development of allergic airway disease is controversial. On the one hand, CD8(+) T cells are known to inhibit the development of airway hyperreactivity (AHR) in murine models of asthma. In humans, IL-10-producing CD8(+) T cells were shown to act as regulatory cells, inhibiting both proliferation and cytokine secretion of T cells. On the other hand, CD8(+) T cells can promote IL-5-mediated eosinophilic airway inflammation and the development of AHR in animal models. To examine this, we investigated the role of CD8(+) T cells during the induction of allergen-induced AHR and demonstrated a protective effect of CD8(+) T cells. Depletion of CD8(+) T cells prior to the immunization led to increased Th2 responses and increased allergic airway disease. However, after development of AHR, CD8(+) T cells that infiltrated the lungs secreted high levels of IL-4, IL-5 and IL-10, but little IFN-gamma, whereas CD8(+) T cells in the peribronchial lymph nodes or spleen produced high levels of IFN-gamma, but little or no Th2 cytokines. These data demonstrate protective effects of CD8(+)T cells against the induction of immune responses and show a functional diversity of CD8(+) T cells in different compartments of sensitized mice.     

Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen-induced Th2 responses, airway inflammation and airway hyper-reactivity in mice

BACKGROUND: Allergen-induced sensitization and airway disease are the results of adverse immune reactions against environmental antigens that may be prevented or inhibited by immune modifying strategies. OBJECTIVE: To investigate the effects of the novel immune response modifier resiquimod (R-848), from the family of imidazol-derivates, in a murine model of allergen-mediated Th2-immune responses and concomitant airway inflammation and airway hyper-reactivity. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) on days 1 and 14 and challenged with OVA aerosol on days 28 and 29. R-848 was applied intranasally to sensitized animals once prior to the first allergen airway challenge, on day 27. RESULTS: A single application of R-848 significantly reduced numbers of eosinophils and lymphocytes in bronchoalveolar lavage fluid and inhibited mucus gland hyperplasia, compared with sensitized and challenged controls. Associated with the decrease in airway inflammation, single intranasal treatment with R-848 abolished the development of airway hyper-reactivity after allergen sensitization and airway challenges. Additionally, Th2-cytokine production in lung tissues from sensitized and R-848-treated animals was reduced, whereas IL-12 and IFN-gamma production was increased, compared with non-treated sensitized mice. CONCLUSION: These data indicate that R-848 effectively inhibits allergen-induced airway inflammation and hyper-reactivity by modulation of increased Th2-immune responses.