Increased Frequencies of Th22 Cells as well as Th17 Cells in the Peripheral Blood of Patients with Ankylosing Spondylitis and Rheumatoid Arthritis

<div><h3>Background</h3><p>T-helper (Th) 22 is involved in the pathogenesis of inflammatory diseases. The roles of Th22 cells in the pathophysiological of ankylosing spondylitis (AS) and rheumatoid arthritis (RA) remain unsettled. So we examined the frequencies of Th22 cells, Th17 cells and Th1 cells in peripheral blood (PB) from patients with AS and patients with RA compared with both healthy controls as well as patients with osteoarthritis.</p> <h3>Design and Methods</h3><p>We studied 32 AS patients, 20 RA patients, 10 OA patients and 20 healthy controls. The expression of IL-22, IL-17 and IFN-γ were examined in AS, RA, OA patients and healthy controls by flow cytometry. Plasma IL-22 and IL-17 levels were examined by enzyme-linked immunosorbent assay.</p> <h3>Results</h3><p>Th22 cells, Th17 cells and interleukin-22 were significantly elevated in AS and RA patients compared with OA patients and healthy controls. Moreover, Th22 cells showed positive correlation with Th17 cells as well as interleukin-22 in AS and RA patients. However, positive correlation between IL-22 and Th17 cells was only found in AS patients not in RA patients. In addition, the percentages of both Th22 cells and Th17 cells correlated positively with disease activity only in RA patients not in AS patients.</p> <h3>Conclusions</h3><p>The frequencies of both Th22 cells and Th17 cells were elevated in PB from patients with AS and patients with RA. These findings suggest that Th22 cells and Th17 cells may be implicated in the pathogenesis of AS and RA, and Th22 cells and Th17 cells may be reasonable cellular targets for therapeutic intervention.</p> </div

Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments) and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA).FCT fellowship: (SFRH/BPD/92860/2013)

Th17 cytokines and arthritis

Th17 cells are implicated in human autoimmune diseases, such as rheumatoid arthritis (RA), although it has not been established whether this persistent destructive arthritis is driven by Th1 and/or Th17 cells. Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis as has been shown in several experimental arthritis models. Importantly, recent data from first clinical trials with anti-IL-17A antibody treatment in psoriatic arthritis patients and RA patients looks promising. This review summarizes the findings about the role of Th17 cells in arthritis and discusses the impact of the different Th17 cytokines in the pathogenesis of this disease. However, further studies are needed to unravel the interplay between IL-17A and other Th17 cytokines such as IL-17F, IL-22, and IL-21 in the pathoimmunological process of this crippling disease, in particular, whether regulating Th17 cell activity or specific combinations of Th17 cytokines will have additional value compared to neutralizing IL-17A activity alone. Moreover, tumor necrosis factor-positive Th17 cells are discussed as potential dangerous cells in driving persistent arthritis in human early RA

Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.

Contains fulltext : 97228.pdf (publisher's version ) (Open Access)BACKGROUND: Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. METHODS: Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-alpha treatment as a marker of RA severity was assessed. RESULTS: The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. CONCLUSIONS: We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA

Elinsiirron saaneen nuoren siirtyminen lasten ja nuorten hoitotyöstä aikuisten terveyspalveluiden käyttäjäksi

Opinnäytetyömme tarkoituksena on kuvata saumaton, hoitoon sitoutumista tukeva hoitopolku nuoren elinsiirtopotilaan siirtyessä lasten ja nuorten hoitotyöstä aikuisten terveyspalvelujen käyttäjäksi. Työmme on osa lasten ja nuorten hoitotyön osaamisen tulevaisuuden hanketta. Hankkeen tarkoituksena on uusien toimintakäytäntöjen luominen, verkostomaisen työskentelyn vahvistaminen, sekä saumattomien hoitopolkujen kehittäminen. Hankkeessa yhteistyökumppaneina ovat HYKS Naisten- ja lastentautien tulosyksikkö, Metropolia ammattikorkeakoulun Hoitotyön koulutusohjelma ja Tampereen yliopiston Hoitotieteen laitos. Työssämme keskitymme potilaan siirtymävaiheen solmukohtiin, kuvaamme nykyisen hoitopolun ja pyrimme löytämään näkökulmia sekä toimintamalleja, jotka antaisivat nuorelle, hänen perheelleen sekä hoitoyksikölle valmiuksia siirtymisprosessin vaiheisiin. Työssämme keskitymme nuorten kehittymishaasteisiin ja pyrimme kartoittamaan nuorten hoitomyönteisyyttä ja vastaanottavaisuutta edistäviä keinoja ja välineitä. Opinnäytetyömme aihe on uusi hoitotieteellisen tutkimuksen kohde ja löytämämme materiaali on luonteeltaan täsmällistä, tuoretta ja vastaa hyvin työmme edistymisen vaateisiin. Käytimme työssämme kvantitatiivista tutkimusmenetelmää. Tutkimustyön tarve sekä prosessin kehittäminen potilaan tarpeita vastaavaksi tällä hoitotyön saralla on erittäin tärkeää. Kansainvälisesti siirtymisessä koetaan haastavimmaksi prosessin alkamisen äkillisyys, riittämätön tiedonkulku lasten ja aikuisten puolen välillä ja tätä kautta hoidon jatkuvuuden kankeus. Toisin sanoen siirtymiseen valmistavien toimintojen aikaistaminen, kirjallinen informaatio ja sujuvampi yhteistyö palveluiden tarjoajien välillä, ovat suurimmat kehittymishaasteet

Augmented levels of macrophage and Th1 cell-related cytokine mRNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflammation of the salivary and lachrymal glands resembling Sjögren's syndrome (SS), representing an animal model to study this disease. We used in situ hybridization with synthetic radiolabelled oligonucleotide probes to examine expression of mRNA encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4 and 5-month-old MRL/lpr mice. Phenotypic composition of submandibular gland infiltrates was evaluated by immunohistochemistry. Cells expressing tumour necrosis factor-alpha (TNF-α), IL-1β, IL-6 and IL-12 mRNA were strongly up-regulated at about the time of onset of sialoadenitis, suggesting a role of these cytokines in development of the disease. Interferon-gamma (IFN-γ) and cytolysin mRNA-expressing cells were gradually up-regulated over the disease course up to 5 months of age, the time when sialoadenitis is at its height, favouring a role of these cytokines in progression of the disease as well. Low levels of IL-10 and transforming growth factor-beta (TGF-β) mRNA-expressing cells were observed at 2, 3 and 4 months of age, and were almost undetectable at 5 months. Maximum levels of CD4+, CD8+ and interdigitating/dendritic cells, as well as of MHC class II and MHC class I expression were seen at 3 months, with CD4+ outnumbering CD8+ cells. Maximum levels of macrophages were seen at 4 months of age. These data argue for a major role of the proinflammatory cytokines TNF-α, IL-1β, IL-6, IL-12, IFN-γ and cytolysin in initiation and perpetuation of autoimmune sialoadenitis in MRL/lpr mice, probably in conjunction with an insufficiency of the anti-inflammatory cytokines TGF-β and IL-10