Biochemical and genetic risk factors for atherosclerosis in systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is associated with an increase in the risk of premature cardiovascular complications caused by accelerated atherosclerosis which significantly contributes to morbidity and mortality. Carotid ultrasonography is a very sensitive imaging tool to detect premature atherosclerosis and measurements of carotid intima-media thickness [IMT] assess the extent and the severity of systemic atherosclerosis. The pathogenesis of accelerated atherosclerosis in SLE is not clear; inflammation and endothelial dysfunction in addition to genetic risk factors represent important factors in the onset of atherosclerosis. To evaluate the relation between asymmetric dimethylarginine [ADMA], high sensitive C-reactive protein [hs-CRP], monocyte chemoattractant protein-1 [MCP-1] [both serum levels and the genotypes of the MCP-1 A-2518G polymorphism] with the development of carotid atherosclerosis in patients with SLE and their relation to disease activity. In the present study, 30 non-menopause SLE female patients and 20 healthy age-matched females were included. Both patients and controls were subjected to evaluation of body mass index [BMI], IMT, serum glucose, serum lipids, hs-CRP, ADMA, MCP-1 [both serum level and gene polymorphism]. Serum ADMA, hs-CRP, and MCP-1, levels were measured by enzyme-linked immunosorbent assay. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Values for IMT, hs-CRP, ADMA and MCP-1 were significantly higher in patients with SLE than in healthy controls with more significant increase in SLE patients with IMT >/=1 mm than in those with IMT <1 mm. Carotid IMT was significantly positively correlated with all the studied variables except for age, BMI and FBS, but significantly negatively correlated with HDL-C in all SLE patients. G/G genotype of MCP-1 A-2518G gene was more frequent in SLE patients than controls. IMT, hs-CRP, ADMA and MCP-1 from patients with G/G phenotypes were markedly higher than those from patients with the A/A genotype. In multiple regression analysis, ADMA and MCP-1 were the strongest independent determinants of IMT in SLE patients. Assessment of high levels of ADMA, hs-CRP, MCP-1, in addition to the MCP-1 A-2518G polymorphism may play a role in the pathogenesis of accelerated atherosclerosis in SLE patients and would be useful in identifying the risk of developing cardiovascular disease. Development of a novel therapy targeting ADMA and MCP-1 may have a potential role in preventing the progression of increased IMT in SLE patients

Central role of IL-10 as key regulator of inflammation during intestinal trichinellosis in mice

This study characterized some immuno-pathological aspects of intestinal trichinellosis where, the influence of this nematode infection on levels of IL-10 mRNA expression, nitric oxide [NO] and myeloperoxidase [MPO] in intestinal mucosa is going to be studied. Four groups of albino mice were infected orally by Trichinella spiralis [T. spiralis] larvae and sacrificed on days 3, 6, 14, and 30 post infections [d.p.i.]. Levels of the previously mentioned parameters were measured in the infected intestinal tissue samples and compared to non-infected normal controls. The results showed gradual increase of IL-10 mRNA expression at 3 d.p.i., to reach its peak levels at 14 d.p.i. The mucosal levels of NO and MPO showed sharp increased by 3[rd] d.p.i., with a peak on 6 d.p.i. These biochemical changes were in accordance with the pathological changes observed by histopathological examination of stained small intestinal sections. The data reinforce the concept of the central role played by IL-10, as a Th2 cytokine in controlling severe inflammatory process initiated by NO under the influence of this invading parasite