SummaryAnalysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame ofHerpesvirus saimiri. Here we report on the cloning of human , the human counterpart ofmurine IL-17. hlL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4 + T cells. Although devoid of direct effects on cells of hematopoietic origin, hlL-17 and the product of its viral counterpart, Olq.F13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte--colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hlL-17, fibroblasts could sustain the proliferation of CD34 + hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hlL-17 may constitute (a) an early initiator of the T cell-dependent inflammatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.T lymphocytes produce an array of small proteins that are involved in cell growth, inflammation, immunity, differentiation, and repair. These protein mediators referred to as cytokines are not produced constitutively by T cells, but rather are induced after receptor-mediated T cell activation (1, 2). Murine cytotoxic T lymphocyte associated antigen-8 (mCTLA8) 1, a cDNA previously cloned by lq.ouvier et al. (3) from a T cell subtraction library, displays some of the features ofa cytokine gene: in particular, a pre1Abbreviations used in this paper: hlL-17, human IL-17; HVS, Herpesvirus saimiri; ORF13, open reading frame 13; mCTLA8, murine cytotoxic T lymphocyte-associated antigen 8; PGE 2, prostaglandin E2; PI, PMA and ionomycin.Parts of this work were presented at

Recent studies indicate that interleukin 8 (IL-8) production contributes to the host immune responses against mycobacterial infection. In this study, we were interested to determine whether induction of IL-8 in human monocytes infected with Mycobacterium bovis was regulated by other monocyte-derived cytokines important in antimycobacterial immunity: IL-10 and transforming growth factor ␤ (TGF-␤). Here, we report that IL-10 reduced, in a graded and significant manner, IL-8 production by M. bovis-infected human monocytes. Additionally, the specificity of the observed inhibition was further confirmed, since the addition of an anti-IL-10 neutralizing antibody completely reversed the inhibitory effect. In contrast, addition or neutralization of TGF-␤ appeared to have no significant effect on M. bovis-induced IL-8 secretion by human monocytes, whereas CD40 expression on M. bovis-infected monocytes was significantly inhibited by this cytokine. This was consistent with the finding by the reverse transcription-PCR method that pretreatment with IL-10, but not TGF-␤, potently inhibited IL-8 mRNA levels. Interestingly, neutralization of endogenous IL-10 did not significantly alter IL-8 secretion, suggesting that induction of IL-8 was not significantly affected by coexpression of IL-10 during infection of human monocytes with M. bovis. Collectively, these data indicate that IL-8 production may be regulated when human monocytes are exposed to IL-10 prior to activation with M. bovis BCG. These data will aid in our understanding of the mechanisms involved in regulating the protective immune response to stimulation with M. bovis BCG.

BackgroundIn the management of rheumatologic patients treated with intravenous therapies, its regular monitoring is recommended in order to ensure its safety. The Nursing Consultation for monitoring rheumatologic patients treated with Intravenous Therapies (NCIT) represents a major support to patient caring for it provides patient monitoring before treatment administration and prior to rheumatologist consultation.ObjectivesTo analyze number and types of incidents detected in the NCIT.MethodsA cross-sectional longitudinal, observational study of data from patients followed-up in the NCIT (which was initiated in 2012) was performed. We have collected data of gender, diagnosis, drug administered, incidents detected previously to the drug administration, and if the incident was detected by telephone (one day before drug administration) or by personal interview. Biostatistical analysis with R (3.3.2.) was performed.ResultsWe analyzed 7809 drug infusions corresponding to 545 patients (73% women). 48.25% of patients were diagnosed with osteoporosis (OP), 30.1% rheumatoid arthritis (RA), 5.7% ankylosing spondylitis (AS), 4.2% systemic lupus erythematous (SLE), 2.9% psoriatic arthritis (PsoA) and 8.3% had other diagnosis. The intravenous therapies were antiosteoporotic drug (7.8%) and biological and immunosuppressive treatment, being the most common drugs tocilizumab (38.89%), infliximab (31.9%) and abatacept (18.05%). In the 7809 treatment infusions, 477 incidents (4.1%) were registered, 33 of them related to the antiosteoporotic therapies and the other 444 incidents (93%) occurred in the biological therapies. The 63.7% of the incidents were detected by telephone one day before drug infusion. Statistical analysis showed that SLE patients exhibit higher tendency to incidents (4.8% of incidents in the 392 treatments for SLE patients; P=0.026) than other autoimmune diseases. On the other hand, RA and AS patients have incidents detected mainly by telephone ((P=0.047 y P=0.029 respectively). We also observed a high number of incidents in the intravenous administration of TCZ (P=0.009).ConclusionsThe NCIT has performed the follow-up of more than 5oo patients with only 6% of incidents, contributing to an improvement in the patients' health and in its caring. Moreover, the fact of identifying the incidents helps to reduce the number of personal consultations, avoids drug preparation in those cases where this infusion is suspended, and in summary it improves management of hospital resources.Disclosure of InterestNone declared

BackgroundCrohn's disease (CD) and ulcerative colitis (UC) are the main entities of inflammatory bowel disease (IBD). Both present extraintestinal manifestations that do not always depend on the IBD activity. The most common manifestations involve the musculoskeletal system and they are included in the seronegative spondiloarthritis group. If there is active or known IBD, treatment of this is priority because it usually improves joint disease. However, joint disease can also have an independent course of the intestinal manifestations as in patients with IBD and ankylosing spondylitis (AS).ObjectivesTo analyze the prevalence of extraintestinal manifestations in IBD patients and treatment provided.MethodsRetrospective observational analysis of IBD patients that have been remitted to the rheumatology department of HUP La Fe with musculoskeletal manifestations. Demographic, clinical and treatment data of patient were collected. Biostatistical analysis with R (3.3.2.) was performed.ResultsWe recruited 183 patients diagnosed with IBD (57.4% women), 117 with CD and 66 with UC, with a mean age at diagnosis of 37.03±14.02 years old. 29 of them have axial affection and 51 peripheral affection, and simultaneously in 22 cases. We observed no statistical differences in axial or peripheral affection according to the IBD diagnosis. 79 cases were on biological therapy, and these treatments were conducted by Rheumatology in the 44% of cases and by Digestive Department in the 66% of cases. We observed that patients with axial affection present higher probability that the treatment has been conducted by Rheumatology (P=0.007), and broken down axial affections AS diagnosis had the most probability to be conducted by Rheumatology (n=36 P=0.0102). Related to peripheral manifestations, uveitis diagnosis had the most probability to be conducted by Rheumatology (n=14 P=0.0337).ConclusionsIn our patient series with IBD and musculoskeletal manifestations, the most common were peripheral affection. Among patients with IBD and axial and/or peripheral manifestation, 44% were conducted by Rheumatology, and are cases with axial predominance, where IBD treatment does not improve musculoskeletal disease and a primary spondyloarthritis treatment is needed.Disclosure of InterestNone declared

BackgroundSystemic lupus erythematous (SLE) shows increased DNA demethylation. An intermediate step to DNA demethylation is the DNA hydroxymethylation, where 5-mC is oxidized into 5-hmC. Hydroxymethylation is not completely understood and it may be related to oxidative stress in SLE patient.ObjectivesTo analyze the association between the hydroxymethylation and demethylation, with the antioxidant response and SLE pathophysiology.MethodsWe analyzed in 142 SLE patients and 34 healthy controls the serum concentration of glutathione (GSH) and glutathione disulphide (GSSG) by UPLC-MS/MS, superoxide dismutase (SOD) and total antioxidant capacity (TAC) by colorimetric methods. 5-mC and 5-hmC levels were measured by colorimetric methods. Complete blood-test was made and clinical data by personal interview was collected. Biostatistical analysis with R (3.3.2.) was performed.ResultsThere is a correlation between the methylation and hydroxymethylation rate (P<0.001), and both were lower in patients than in controls (P=0.024; P<0.001). GSH and GSSG values were lower in patients (P=0.033 y P=0.003), but GSH/GSSG ratio was not statistically different in both groups. SOD levels were higher in patients (P=0.001), but TAC did not show significant differences. Higher demethylation is associated to lower TAC values in patients and healthy controls (P=0.005; P=0.01). In patients, decreased SOD values are associated with higher demethylation and lower hydroxymethylation rates (P<0.001; P=0.007). SOD and TAC levels are increased in SLE patients with higher demethylation and lower hydroxymethylation (P=0.001; P<0.001). We did not observe any association between 5-mC or 5-hmC levels and GSH, GSSG or GSH/GSSG ratio. Higher demethylation is associated to vascular symptoms (defined by RELESSER study) and lupus anticoagulant (AL) positivity (P=0.041; P=0.015), and lower hydroxymethylation to mucocutaneous damage (defined by RELESSER study) and AL positivity (P=0.015; P=0.009). Lower levels of GSH and GSSG were associated to increased accumulated damage assessed by SLICC (P=0.01; P=0.005), and lower SOD values with longer disease duration (P=0.001).ConclusionsWe observed higher demethylation and lower hydroxymethylation in SLE patients than in controls, related to increased SOD activity. Moreover higher demethylation leads to lower TAC levels. These epigenetic disorders are related to antioxidant response disruptions in SLE patients, probably because of the chronic inflammatory condition. Our results suggest that epigenetic processes are involved in SLE physiopathology.AcknowledgementsFinancial support by GVA (GV15/83) is acknowledged.Disclosure of InterestNone declared