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Background Cardiovascular complications are the most serious ones associated with lupus, and are thought to be caused by inflammation which results from autoimmunity. This study uses a metabolomic screen to identify metabolites that are elevated in SLE patients with and without CVD. Four of metabolites elevated in the initial screen have been selected for validation by ELISA. Methods 27 serum samples (10 healthy controls, 8 with SLE and plaque progression, 9 with SLE and no plaque progression) were screened for elevated metabolites. Four of the most significantly elevated metabolites were selected for validation in another cohort of 85 serum samples (25 healthy controls, 53 with lupus nephritis, 7 with both lupus nephritis and cardiovascular disease). Results Metabolomic screening of the initial cohort demonstrated that several lipoxygenase metabolites (and HODE 13) were elevated in SLE patients who developed CVD compared to other SLE patients (p < .05) and healthy controls (p < .05). Based on this, LOX15, LTB4, and PLA2G7 (as well as HODE13) were selected for ELISA validation. Serum PLA2G7 correlated positively with number and increase of atherosclerotic plaques, as well as smoking history (p Conclusions Serum LTB4, HODE13 and PLA2G7 exhibit potential as biomarkers distinguishing between SLE patients who are or are not at risk of developing cardiovascular complications. Longitudinal studies are in progress to assess the clinical utility of these novel markers.

Background Given the potential side effects associated with conventional medical treatment of Inflammatory Bowel Disease (IBD), dietary supplements have been investigated by several groups. We tested if epigallocatechin gallate (EGCG) may be beneficial in IBD. Methods 36 C57BL/6J mice were subjected to dextran sulfate sodium (DSS)-induced IBD and divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg /kg/d). Results Both high and low dose EGCG treatment alleviated clinical manifestations of IBD including body weight loss and disease activity index (DAI): HE: 3.3 and LE: 2.8 vs. 8.3 in MD (p < 0.001, n=8–10 mice/group). Macroscopic severity score (MSS) of HE and LE groups were 2.4, and 2.2, respectively, significantly lower than in MD (5.0, P < 0.01). The mean colon length of MD group was 5.8 cm; treatment with EGCG restored colon length (HE: 6.5 cm; LE: 6.4 cm). Intestinal permeability was improved as demonstrated by FITC-Dextran assay (HE: 3.28; LE: 2.85, vs. MD group: 6.69 ng/ml, P < 0.001) .The colitis histology score of HE (1.54) and LE (0.42) groups were significantly lower than that in MD (4.3, P < 0.001). In addition, EGCG treatment reduced colonic levels of pro-inflammatory cytokines: IL-6 (HE: 0.45; LE group: 0.41 vs MD: 0.89 ng/g tissue, P =0.03), MCP-1 (HE: 1.83; LE: 1.87, vs MD: 3.5 ng/g tissue P = 0.01) and TNF-alpha (HE: 8.87; LE: 10 vs MD: 21.7 ng/g tissue, P Conclusion These results underscore the therapeutic potential of EGCG in the treatment of IBD, which appear to be mediated through multiple inflammatory pathways.

Background Here, we examine the therapeutic efficacy of Epigallocatechin-3-gallate, the most potent catechin in green tea, on nonalcoholic fatty liver disease (NAFLD), a growing epidemic in humans. Methods NAFLD was induced by high-fat diet (HFD) with 30% fructose in drinking water for 8 weeks. Mice were divided into 3 groups: model group (MD; no EGCG), low dose EGCG group (LE, 20 mg/kg/d) and high dose EGCG group (HE, 50 mg/kg/d). Liver histology, serum lipid prolife, liver function as well as liver M1/M2 polarization were evaluated. Results At the end of the experiment, the mean body weight of LE and HE mice were 39.7g and 45.7g, while it was 51.9g in the MD group (P< 0.05). Similarly, liver weights in the LE and HE groups (means = 1.44g, and 1.68g, respectively) were lower than that in MD (2.94g, P < 0.01). Liver dysfunction observed in the MD group (mean AST=133.2 U/L and ALT=183.4 U/L), was significantly improved in both LE (44.8 U/L, 86.8 U/L, respectively, P < 0.001) and HE groups (83.63 U/L, 117.6 U/L, respectively P < 0.05). Serum cholesterol, HDL, triglyceride levels were increased in the MD group, but lowered in both LE and HE mice (p Conclusion EGCG subdued NAFLD despite consumption of HDF and high fructose water, marked by improved liver function and serum lipid profile, as well as M1/M2 polarization. EGCG should be investigated as a therapeutic modality in human NAFLD.

Background Rheumatoid arthritis is an autoimmune disorder in which the immune system attacks its own tissues, resulting in swelling and inflammation of the joints. Hemopexin (Hx), an acute-phase protein synthesized by hepatocytes in response to proinflammatory cytokines, binds to heme, and controls heme-iron availability in tissues and T lymphocytes. Its absence has been associated with increased inflammatory properties of high-density lipoproteins and the development of autoimmune disease, such as experimental autoimmune encephalomyelitis (EAE). The aim of this study is to investigate the role of Hx in the development of arthritis using the collagen antibody-induced arthritis (CAIA) mouse model. Methods CAIA was induced in Hx-deficient (Hx−/−) mice and wild-type (WT) littermates, via i.p injection of antibodies directed against type II collagen, followed by the administration of lipopolysaccharide (LPS). Paw thickness and disease severity was evaluated daily. Blood samples were collected to measure the serum Hx levels using ELISA. Results During CAIA, serum Hx level became elevated and remained high. When CAIA was induced in Hx−/− mice, they exhibited reduced arthritis compared to WT mice, as arthritic Hx−/− mice had lower average paw thickness (1.32 ± 0.02 vs 2.67 ± 0.05, 2-tail t test, P < 0.05 ) and reduced arthritis scores ( 2.0 ± 0.5 vs 7.3 ±1.25, 2-tail t test, P < 0.01) at the end of the experiment compared to WT mice. Pathology studies are in progress. Conclusion Hx−/− mice are protected from CAIA, with reduced arthritis, indicating a pro-inflammatory role for Hx in the development of arthritis. Further studies are warranted to unravel the pathogenic mechanisms involved and clinical relevance of this molecule.