The Role of Chemokines in Mediating Graft Versus Host Disease: Opportunities for Novel Therapeutics

Bone marrow transplantation (BMT) is the current therapy of choice for several malignancies and severe autoimmune diseases. Graft versus host disease (GVHD) is the major complication associated with BMT. T lymphocytes and other leukocytes migrate into target organs during GVHD, become activated and mediate tissue damage. Chemokines are well known inducers of leukocyte trafficking and activation and contribute to the pathogenesis of GVHD. Here, we review the major animal models used to study GVHD and the role of chemokines in mediating tissue damage in these models. The role of these molecules in promoting potential beneficial effects of the graft, especially graft versus leukemia, is also discussed. Finally, the various pharmacological strategies to block the chemokine system or downstream signaling events in the context of GVHD are discussed

Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients

OBJECTIVE: This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia. METHOD: We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-a), two soluble TNF-a receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2-3 ml of plasma was obtained from each blood sample and stored at -80°C. RESULTS: The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1. CONCLUSION: Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints

The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases

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Eosinophil recruitment into sites of delayed‐type hypersensitivity reactions in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142239/1/jlb0353.pd

Exploiting the pro-resolving actions of glucocorticoid-induced proteins Annexin A1 and GILZ in infectious diseases.

For decades, glucocorticoids (GC) have been used to treat several inflammatory conditions, including chronic and autoimmune diseases, due to their potent anti-inflammatory properties. In the context of infectious diseases, the use of GCs may be effective as adjuvant to antibiotic therapy by controlling excessive inflammatory responses resulting in better outcome in some cases. However, the use of GCs has been associated with a vast number of side effects, including increased probability of immunosuppression and consequent risk of opportunistic infection. Glucocorticoid-induced leucine zipper (GILZ) and Annexin A1 (AnxA1) are GC-induced proteins intrinsically involved with the anti-inflammatory functions of GCs without the associated adverse metabolic effects. Recent studies have shown that these GC-proteins exhibit pro-resolving effects. An essential characteristic of pro-resolving molecules is their ability to coordinate the resolution of inflammation and promote host defense in most experimental models of infection. Although the role of GILZ and AnxA1 in the context of infectious diseases remain to be better explored, herein we provide an overview of the emerging functions of these GC-proteins obtained from pre-clinical models of infectious diseases

Effects of Xylopia aromatica (Lam.) Mart. fruit on metabolic and inflammatory dysfunction induced by high refined carbohydrate-containing-diet in mice

AbstractObesity is associated with chronic low-grade inflammation, which has been shown to be involved in the development of various comorbidities such as insulin resistance, glucose intolerance and liver damage. Phytochemicals found in some spices could modulate inflammation and improve health problems associated with the excess of adiposity. The extract of the Brazilian pepper Xylopia aromatica (Lam.) Mart. (CEXA) showed positive effects in the lower dose on oral glucose tolerance, hepatic steatosis and liver inflammation. The higher dose of CEXA also showed improvement on insulin sensitivity and release of anti-inflammatory cytokines IL-13 and IL-4 on adipose tissue and liver. Chemical analysis revealed the presence of phenolic acids and flavonoids in CEXA. This study suggests the potential of the Brazilian pepper to attenuate mice glucose resistance and liver inflammation, health problems commonly associated with obesity

Concerns regarding hepatitis B vaccination and post-vaccination test among Brazilian dentists

<p>Abstract</p> <p>Background</p> <p>Hepatitis B infection is the major cause of acute and chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide and has long been recognized as an occupational hazard among dentists. The aim of the present study was to examine factors associated to the self-reporting of hepatitis B vaccination and immunization status among dentists working in the city of Belo Horizonte, Brazil.</p> <p>Methods</p> <p>A cross-sectional survey was carried out with 1302 dentists in Belo Horizonte, Brazil. After signing a term of informed consent, the participants answered a structured questionnaire on their knowledge regarding their vaccination and immunization status against hepatitis B. Data on demographic, behavioural and occupational exposure aspects were also collected through questionnaires.</p> <p>Results</p> <p>The results revealed that 73.8% of the dentists reported having received three doses of the vaccine. Multivariate analysis revealed that gender (p = 0.006), use of individual protective equipment (p = 0.021), history of blood transfusion (p = 0.024) and history of illicit drug use (p = 0.013) were independently associated with vaccination against hepatitis B. Only 14.8% had performed a post-vaccination test. The use of individual protective equipment (p = 0.038), dentists who asked patients about hepatitis during dental treatment (p < 0.001), a family history of hepatitis B (p = 0.003) and work experience (p < 0.05) were independently associated with the post-vaccination test.</p> <p>Conclusions</p> <p>Although there were a large number of vaccinated dentists in Belo Horizonte, the percentage was less than what was expected, as Brazil offers the National Program of Viral Hepatitis Vaccination, which provides free hepatitis B vaccinations to all healthcare workers. Despite being part of a high risk group for contamination, most of the dentists did not know their immunization status.</p

Factors associated with seroprevalence of hepatitis C among dentists at a large Brazilian city

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to investigate the seroprevalence and sociodemographic data, health-related and occupational factors and other correlates of sero-posivity among dentists in the city of Belo Horizonte, MG, Brazil.</p> <p>Methods</p> <p>A cross-sectional survey was carried out with 1302 dentists in Belo Horizonte, Brazil. All dentists were tested for anti-HCV using a commercially available enzyme-linked immunosorbent assay (ELISA). Individuals positive for anti-HCV were recalled for further evaluation. The presence of HCV RNA in anti-HCV-positive samples was assessed using reverse transcription-polymerase chain reaction (RT-PCR). Data on demographic, behavioural and occupational exposure aspects were collected through questionnaires.</p> <p>Results</p> <p>The seroprevalence of anti-HCV was 0.9% (95% IC 0.5-1.7%). The factors associated to the prevalence of hepatitis C were history of blood transfusion (p = 0.002) and having undergone a test for hepatitis C (p = 0.015).</p> <p>Conclusions</p> <p>The seroprevalence of anti-HCV among dentists is low. Moreover, no occupational exposure was associated to the seroprevalence of hepatitis C.</p

Resolution of inflammation: Mechanisms and opportunity for drug development

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The role of CCL22 (MDC) for the recruitment of eosinophils during allergic pleurisy in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142274/1/jlb0356.pd