Additional file 2: Figure S2. of Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1β production

Immunoglobulin production of WT and IL-22−/− mice. Levels of total IgG (A) and IgG2a (B) antibodies against mBSA in the sera of WT and IL-22−/− mBSA-immunized mice. Data are the means ± SEM (n = 5). (TIFF 1185 kb

Additional file 4: Figure S4. of Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1β production

The inflammasome adapter ASC participates in articular hypernociception and neutrophil migration that are induced by IL-22 during AIA. (A) The concentrations of IL-1β in the knee joint injected with 1 ng of IL-22 or saline and pretreated with fucoidin (20 mg/kg, i.v. 15 min before stimuli injection) in mBSA-immunized mice were determined 3 h after the challenge. (B) Articular hypernociception was evaluated 1–7 h after i.a. injection with either IL-22 (1 ng per joint) or saline in mBSA-immunized WT or ASC−/− mice. (C) Neutrophil recruitment toward the articular cavity 7 h after i.a. administration of IL-22 (1 ng) or saline in mBSA-immunized WT or ASC−/− mice. Data are presented as the means ± SEM (n = 5). * P < 0.05, compared with the saline group; and # P < 0.05, compared with the vehicle (−)/WT IL-22 groups. (TIFF 930 kb

Additional file 3: Figure S3. of Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1β production

Role of IL-22 in zymosan-induced arthritis. (A and B) WT or IL-22−/− mice were challenged i.a. with zymosan (30 μg per joint) or saline and articular hypernociception (A) and neutrophil migration (B) were evaluated 7 h after the challenge. Data are presented as the means ± SEM (n = 5). * P < 0.05, compared with the saline group. (TIFF 1105 kb

Additional file 6: Figure S3. of Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

Serum levels of GPT and AST in LAP-treated mice during CIA protocol. (PDF 518 kb

Additional file 2: TableS1. of Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

LAP and LAP sodium salt pharmacokinetic parameters determined by noncompartmental and compartmental approaches after i.v. administration of 2 mg/kg in Wistar rats. (PDF 93 kb

Additional file 5: Table S3. of Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

Evaluation of the toxicity of lapachol in proliferating CD4 T cells. (PDF 224 kb

Additional file 1: Figure S1. of Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

Mean concentration–time profiles of lapachol after (A) 2 mg/kg i.v., (B) 10 mg/kg oral, and (C) 25 mg/kg oral administration to rats. Data points are mean ± standard deviation. (PDF 146 kb

Additional file 4: Figure S2. of Lapachol, a compound targeting pyrimidine metabolism, ameliorates experimental autoimmune arthritis

Superimposition of the crystallographic hDHODH inhibitor A771726 (PDB id:1D3H, carbon atoms in cyan) and the top-ranked docking solution (carbon atoms in yellow), inside the active site. (PDF 458 kb

TIMP1 and MMP9 are predictors of mortality in septic patients in the emergency department and intensive care unit unlike MMP9/TIMP1 ratio: Multivariate model

<div><p>Introduction</p><p>Matrix metalloproteinases and tissue inhibitors of metalloproteinases could be promising biomarkers for establishing prognosis during the development of sepsis. It is necessary to clarify the relationship between matrix metalloproteinases and their tissue inhibitors. We conducted a cohort study with 563 septic patients, in order to elucidate the biological role and significance of these inflammatory biomarkers and their relationship to the severity and mortality of patients with sepsis.</p><p>Materials and methods</p><p>A multicentric prospective cohort was performed. The sample was composed of patients who had sepsis as defined by the International Conference 2001. Serum procalcitonin, creatinine, urea nitrogen, C-Reactive protein, TIMP1, TIMP2, MMP2 and MMP9 were quantified; each patient was followed until death or up to 30 days. A descriptive analysis was performed by calculating the mean and the 95% confidence interval for continuous variables and proportions for categorical variables. A multivariate logistic regression model was constructed by the method of intentional selection of covariates with mortality at 30 days as dependent variable and all the other variables as predictors.</p><p>Results</p><p>Of the 563 patients, 68 patients (12.1%) died within the first 30 days of hospitalization in the ICU. The mean values for TIMP1, TIMP2 and MMP2 were lower in survivors, MMP9 was higher in survivors. Multivariate logistic regression showed that age, SOFA and Charlson scores, along with TIMP1 concentration, were statistically associated with mortality at 30 days of septic patients; serum MMP9 was not statistically associated with mortality of patients, but was a confounder of the TIMP1 variable.</p><p>Conclusion</p><p>It could be argued that plasma levels of TIMP1 should be considered as a promising prognostic biomarker in the setting of sepsis. Additionally, this study, like other studies with large numbers of septic patients does not support the predictive value of TIMP1 / MMP9.</p></div

Mean laboratory and severity scale values stratified by survival.

<p>Mean laboratory and severity scale values stratified by survival.</p