1,721,166 research outputs found
Pneumopatie interstiziali: aspetti patogenetici e clinici
No full textLe pneumopatie interstiziali sono malattie infiammatorie degenerative del parenchima polmonare caratterizzate da un’iniziale alveolite, unica fase reversibile di queste patologie, conseguente alla redistribuzione cellulare dal sangue periferico al polmone e dalla concomitante proliferazione in situ. Clinicamente, i pazienti presentano dispnea, spesso accompagnata da tosse secca e stizzosa. Accanto ad un’anamnesi e un esame obiettivo accurati, il medico può e deve avvalersi di indagini radiologiche, funzionali e di laboratorio, per definire la diagnosi ed impostare una corretta terapia
Immunologic events in the development of interstitial lung disease: The paradigm of sarcoidosis
No full textAlveolar macrophage - T cell interactions during Th1-type sarcoid inflammation
No full textBACKGROUND:
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined.
METHODS:
Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung.
RESULTS:
Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNgamma(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-gamma, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP.
CONCLUSION:
These data indicate that IFN-gamma mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation
New aspects of hypersensitivity pneumonitis
Full text linkPURPOSE OF REVIEW:
Hypersensitivity pneumonitis (HP) represents a complex pulmonary disorder of varying intensity and clinical presentation, which is characterized by a diffuse Tc1 immune response of lung parenchyma and airways in patients previously sensitized to one of more than 300 etiologic agents that may favor the HP reaction. This review describes recent data that have clarified some of the events that govern the development of the hypersensitivity reaction following exposure to the causative agents involved in this disease.
RECENT FINDINGS:
A number of recent data clearly demonstrate that several cytokines and chemokines, which are secreted at sites of disease activity, participate in the pulmonary inflammatory responses taking place in the lung of patients with HP.
SUMMARY:
The past few years have seen outstanding advances in the understanding of immunologic and molecular events involved in the pathogenesis of HP. It is possible that these data could allow the discovery of therapeutic targets in individuals chronically exposed to HP antigens and evolving towards pulmonary fibrosis
Sarcoidosis is a Th1/Th17 multisystem disorder: wider implications response
No full textWe would like to thank Dr. Parisinos for his letter and interest in our study on the role of Th17 cells in sarcoidosis.[1] His recent report on the development of sarcoidosis in two patients affected by Crohn’s disease (CD) and treated with natalizumab [2] further highlights the deep link existing between the immune pathogenesis of the two disorders. In fact, sarcoidosis and Crohn’s disease are both characterized by an abnormal immune response to still unknown factor(s) that ultimately leads to granuloma formation and tissue damage, and, additionally, in both diseases Th1 and Th17 cytokines coexist and exacerbate the local immune reactions.
Interestingly but not surprisingly, the presence of IL-17 producing T cells further marks out immune-mediated and chronic inflammatory diseases that can coexist with sarcoidosis (systemic lupus erythematosus, autoimmune chronic hepatitis, multiple sclerosis, coeliac disease, ulcerative colitis).
In this context, the use of natalizumab represents an intriguing biological variable not only for its direct function (i.e. the inhibition of the alpha4-mediated adhesion of leukocytes to their counter-receptors) but even for its effects on T cells, particularly the regulatory T cells (Tregs), that are expanded in patients treated with natalizumab.[3] Considering that in presence of proinflammatory cytokines, such as IL-6 (another cytokine shared by sarcoidosis and Crohn’s disease), Tregs convert into Th17 lymphocytes,[4] it could be very interesting to know the levels of Tregs and Th17 cells in the two CD patients described by Parisinos and colleagues
Relationship between stress hormones and immune function at high altitude
No full textWe recently observed that acute and chronic high altitude (HA) exposure can modify number and function of immune cells. As environmental stress condition, hypobaric hypoxia increases hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity; both these systems have been demonstrated to modulate the immune function through cortisol and catecholamines secretion.
PURPOSE: To evaluate possible relationships between stress hormones activation and immunological parameters during acute and chronic HA exposure.
METHODS: 6 healthy moderately active women (mean age 20.6±1.3) reached after 5 days of trekking the Pyramid Laboratory at 5,050 m (Lobuche, Nepal) where stayed for 21 days. Before and after HA exposure (SL1 and SL2), and in the first (P1) and 21th day spent at HA (P2), blood samples for peripheral white blood cells and their subsets, and 24-h urine samples for norepinephrine (NE) epinephrine (E) and cortisol (C), were collected.
RESULTS: During HA exposure (P1 and P2), total lymphocytes significantly decreased in P1 while returned to SL1 values in P2 (from 2.0±0.5x103/ml SL1 to 1.4·103±0.4x103/m P1, p<.05). In particular CD3+ T lymphocytes percentage fell respect to SL1 (from 72.8±6.8 to 54.2±12.4, p<.01 in P1, and to 54.5±12.5 p<.01 in P2), owing to a significant CD4+ T-cell fall (from 50.2±3.9 to 30.8±11.5, p<.01 in P1, and to 35.3±7.9 p<.01 in P2). The percent of Natural Killer cells (NK) (CD16+ and CD56+) significantly increased both in P1 and in P2 (from 15.5±4.4 to 25.2±2.4 p<.01, to 23.3±4.4, p<.01 and from 13.0±6.2 to 26.3±6.8 p<.01, to 21.8±2.7, p<.05, for CD18+ and CD56+, respectively). All these parameters were normalized in SL2, and not significantly different from SL1. Among stress hormones, only NE significantly increased in P1 and in P2 respect to SL values (from 127.4±15.6 to 581.9±219.8 p<.01 and to 737.0±263.5 p<.01, respectively), E showed only a positive trend (p=.08), while cortisol progressively raised reaching a significant increase in P2 (p<.01). CD3+, CD4+ and NK cells demonstrated a large and significant correlation with all three stress hormones, with the strongest correlations observed with NE (R ranged between 0.5 and 0.7).
CONCLUSIONS: Acute and chronic HA exposure affect several cellular immunologic parameters. Their correlations with catecholamines levels suggest a role of sympathetic nervous system in the immune modulation observed during hypobaric hypoxia
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