In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• alveolární makrofágy účinky léků   imunologie   MeSH
• bronchoalveolární lavážní tekutina chemie   MeSH
• chemokin CCL19 MeSH
• chemokin CCL20 MeSH
• chemokiny CC analýza   genetika   imunologie   MeSH
• cyklosporin imunologie   terapeutické užití   MeSH
• dexamethason imunologie   terapeutické užití   MeSH
• dospělí MeSH
• down regulace účinky léků   MeSH
• exprese genu * účinky léků   genetika   imunologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágové zánětlivé proteiny analýza   genetika   imunologie   MeSH
• messenger RNA analýza   MeSH
• plicní sarkoidóza krev   farmakoterapie   imunologie   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• progrese nemoci MeSH
• receptory CCR6 MeSH
• receptory chemokinů * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CCL19 protein, human MeSH Prohlížeč
• CCL20 protein, human MeSH Prohlížeč
• CCR6 protein, human MeSH Prohlížeč
• chemokin CCL19 MeSH
• chemokin CCL20 MeSH
• chemokiny CC MeSH
• cyklosporin MeSH
• dexamethason MeSH
• makrofágové zánětlivé proteiny MeSH
• messenger RNA MeSH
• receptory CCR6 MeSH
• receptory chemokinů * MeSH

INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.

• Klíčová slova
• adverse effects of glucocorticoids, autoimmune diseases, blood cell count, cytokine profile, disease activity, long-treated patients, serum protein pattern, systemic inflammation,
• MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• glukokortikoidy * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * krev   metabolismus   MeSH
• revmatoidní artritida * farmakoterapie   krev   imunologie   MeSH
• senioři MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• glukokortikoidy * MeSH
• mediátory zánětu * MeSH