Intrahepatic interleukin 10 expression modulates fibrinogenesis during chronic HCV infection.

INTRODUCTION: Liver fibrosis is a result of continuous damage to the liver combined with accumulation of the extracellular matrix and is characteristic of most chronic liver diseases such as hepatitis C virus (HCV) infection. METHODS: This study evaluated interleukin 10 (IL10) expression in the liver and plasma of 45 HCV patients and its association with the pathogenesis and progression of liver fibrosis. The expression of transforming growth factor beta (TGFB1) was also assessed. Patients were divided into three groups according to the METAVIR classification (F0-F1, F2 and F3-F4); there was also a control group (n = 8). RESULTS: In the control group, high intrahepatic IL10 mRNA expression showed a positive association with F0-F1 fibrosis, no inflammation, low concentrations of liver enzymes and a high viral load; conversely, low intrahepatic IL10 mRNA expression showed a negative association with fibrosis progression. Intrahepatic TGFB1 mRNA expression was greater in the HCV group than in the control group, and regarding different disease phases, its expression increased as fibrosis evolved to more severe forms. CONCLUSION: Intrahepatic IL10 mRNA expression decreases with persistent fibrosis, probably due to the production of TGF-ß1, a potent antimitotic and fibrogenic cytokine. IL10 restricts and decreases the immune response and limits the fibrogenic response; however, a decrease in IL10 favors persistent inflammatory infiltrate, resulting in severe fibrosis.

Pilates exercise improves the clinical and immunological profiles of patients with human T-cell lymphotropic virus 1 associated myelopathy: A pilot study.

BACKGROUND: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an infectious chronic-inflammatory disease, which can lead to lower limb motions. METHODS: The study evaluated the effects of serial Pilates exercises on the clinical and immunological profiles of patients with HAM/TSP. Eight patients with ages ranging from 39 to 70 years old (2 males and 6 females), 2 wheelchair users and 6 with compromised gait, were evaluated. The patients were submitted to 20 Pilates sessions for 10 weeks. Data were collected at 3 time points (beginning of the study, after Pilates sessions and after 10 weeks without Pilates) and consisted of evaluations of the pain level, spasticity, motor strength, balance, mobility, functional capacity, quality of life and quantification of IFN-γ, IL-10 and IL-9 cytokines levels. RESULTS: After the Pilates sessions, significant improvements in pain level, static and dynamic balance, trunk control, mobility and quality of life were observed, with simultaneous and significant reductions in the serum levels of the cytokines IFN-γ and IL-10. However, after 10 weeks without Pilates, there were significant changes in terms of increasing pain and regression of mobility, with no changes in strength, spasticity, functional capacity in any of the periods of the study. CONCLUSIONS: The results suggest that Pilates may be a promising auxiliary physical therapy for patients with HAM/TSP.

Influence of Immunogenetic Biomarkers in the Clinical Outcome of HTLV-1 Infected Persons.

Human T-lymphotropic virus 1, a member of the Retroviridae family, causes a neglected, silent, persistent infection affecting circa 5 to 10 million people around the world, with biology, immune pathology, clinical diseases, epidemiology, and laboratory issues still unsolved. Most of the infected subjects are asymptomatic, but severe clinical disorders appear as a neurodegenerative disease (HTLV-1 associated myelopathy-HAM) or a lymphoprolipherative disorder (Adult T Leukemia/Lymphoma-ATLL) and in other target organs of the human body. HTLV-1 infections are frequently asymptomatic, but there is a large spectrum of diseases that have been described along the years. The mechanisms by which the virus interacts with the host, the different modes of response of the host to the infection, and the immunogenic characteristics of the host are some of the interesting and unanswered questions that may direct the outcome of the disease. The most relevant published results dealing with the genetic variations of the host, the immune response to HTLV-1 infection, and the outcome of the infection are presented herein, including Human Leucocyte Antigen (HLA), Killer Immunoglobulin-like Receptors (KIR), interleukin 6, 10, 28, Fas and Fas ligand, IFN-gamma, TNF-A, and Mannose-binding lectin. In summary, there are still several unmet research needs in the field of useful biomarkers on HTLV-1 pathogenesis.

HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA Genotype.

The present study investigated the frequencies of rs1800450 (MBL ⁎B, G>A), rs1800451 (MBL ⁎C, G>A), and rs5030737 (MBL ⁎D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification. The genotypic and allelic frequencies showed no significant differences between the groups, but patients with active HBV and the wild AA genotype presented a positive correlation between increased transaminase and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with HCV and the wild AA genotype presented mild inflammation and higher HCV RNA levels, although the same association was not observed for the fibrosis scores. The results suggest that the mutations in exon 1 of the MBL2 gene do not contribute directly to the clinical and laboratory features of HCV and HBV infections, but further studies should be performed to confirm whether the wild AA genotype has indirect effect on disease progression.

In situ detection of Chlamydia pneumoniae, C. trachomatis, and cytokines among cardiovascular diseased patients from the Amazon region of Brazil.

BACKGROUND: Chronic coronary artery disease has been associated, as a consequence of the local inflammatory reaction with previous or persistent infection with Chlamydia pneumoniae, which led to the investigation of the association of cardiovascular disease and previous infection with C. trachomatis and the role of cytokine profile (in situ) markers in the vascular system tissues. METHODS: Sixty-nine biopsies were collected for immunohistochemical analysis for the presence of IL-6, IL-8, TNF-α, IFN-γ, TGF-ß, and IL-10, in 16 fragments from atheromatous plaques, 32 aorta fragments, and 21 valve fragments, using a tissue microarray technique for paraffin embedded tissues. RESULTS: Most patients undergoing revascularization surgery were men >50 years, while those undergoing valve replacement were mostly women <50 years. TNF-α was the most prevalent marker, detected in 91.7% (55/60) of the samples. The mean percent area stained was greater in patients infected with C. pneumoniae (3.81% vs 1.92%; p=0.0115) and specifically in the aorta (4.83% vs 2.25%; p=0.0025); C. trachomatis infection was higher in valves, and C. pneumoniae in plaques, both without statistical significance. There was no significant difference in the cytokine staining profile between patients previously infected with both species and uninfected patients. CONCLUSION: Although there was no difference in the cytokine profile between patients previously infected with both species of Chlamydia, and uninfected patients, the presence of the bacteria antigens in the three biological specimens indicates it is important to focus on the role of C. trachomatis. It is necessary to improve the understanding of the natural history of chronic coronary artery disease and the clinical history of the patients and cytokine dynamics in cardiac disease in the presence or absence of infectious agents.