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Antecedents: The serum levels of some cytokines can be useful in the diagnosis of neonatal sepsis; the prognostic value of a cytokine profile has not, to our knowledge, been explored in this disease. Objective: The objective of this study is to evaluate the diagnostic value of the serum levels of cytokines IL-1, -2, -4, -5, -6, -7, -8, -10, -12, -13, and -17, TNF, IFNγ, G-CSF, GM-CSF, MCP1, and MIP1ß in neonates with high risk of developing sepsis. Methods: Sepsis was evaluated in 96 high-risk neonates. We assessed cytokine levels on hospital admission and during or not during sepsis. Results: Fifty (52%) presented sepsis (26 early and 24 late). Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF. IL-6 values of ≥40.1 pg/mL were associated with the development of any type of sepsis (relative risk [RR]: 1.70; 95% confidence interval [95% CI]: 1.18-2.24; p = .01), while IL-6 values of ≥44.9 pg/mL were associated with early sepsis (RR: 1.29; 95% CI: 1.29-4.56; p = .01). Conclusion: In neonates with high risk for the development of sepsis, there is an association between levels of IL-6, IL-10, and G-SCF and the disease development/outcome.

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Prior exposure to lipopolysaccharides (LPS) induces a state of cell resistance to subsequent LPS restimulation, known as endotoxin tolerance, mainly by repressing the expression of pro-inflammatory cytokines. We established an endotoxin tolerance model in human monocytes Endotoxin-tolerant cells showed a decrease in IκBα degradation and diminished expression of Tumor necrosis factor (TNF) (both messenger RNA [mRNA] and protein content). The myeloid differentiation factor 88 (MyD88)/MyD88 splice variant (MyD88s) ratio, an indirect way to test the Toll-like receptor 4 (TLR4) MyD88-dependent signaling cascade, did not change in endotoxin-tolerant cells when compared to LPS-stimulated or -unstimulated ones. Remarkably, cell population analysis indicated a significant increase of the CD14+ CD16+ subset only under the endotoxin-tolerant condition. Furthermore, endotoxin-tolerant cells produced higher amounts of C-X-C motif chemokine 10 (CXCL10), a typical MyD88-independent cytokine.

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Aspirin-exacerbated respiratory disease is a tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this clinical condition by patients and physicians may have grave consequences because of its association with near-fatal asthma. The pathogenesis of aspirin-intolerant asthma is not related with an immunoglobin E mechanism, but with an abnormal metabolism of the lipoxygenase (LO) and cyclooxygenase (COX) pathways. At present, a diagnosis of aspirin sensitivity can be established only by provocative aspirin challenge, which represents a health risk for the patient. This circumstance has encouraged the search for aspirin intolerance-specific biomarkers. Major attempts have focused on mediators related with inflammation and eicosanoid regulation. The use of modern laboratory techniques including high-throughput methods has facilitated the detection of dozens of biological metabolites associated with aspirin-intolerant asthma disease. Not surprisingly, the majority of these is implicated in the LO and COX pathways. However, substantial amounts of data reveal the participation of many genes deriving from different ontologies. Biomarkers may represent a powerful, noninvasive tool in the diagnosis of aspirin sensitivity; moreover, they could provide a new way to classify asthma phenotypes.

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UNLABELLED: The monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide produced by Entamoeba histolytica in culture. This factor displays several anti-inflammatory properties (i.e., inhibition of locomotion and respiratory burst in monocytes, reduction of skin hypersensitivity and delay of mononuclear cells in human Rebuck skin windows) with inhibition of adhesion molecules, chemokines, and other genes including interleukin-1ß (IL-1ß). In animal models, it reduces carragenin-induced inflammation and delays the inflammatory process in murine collagen-induced arthritis (CIA). OBJECTIVES: To test, in vitro, the anti-inflammatory capacity of MLIF on a promonocytic human cell line (U-937) cells and peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: IL-1ß gene expression was evaluated in cell cultures either in the presence of MLIF, lipopolysaccharide (LPS), or both. Relative gene expression and immunoreactivity of IL-1ß were assayed in cells and supernatants, respectively. RESULTS: Amebic peptide was able to down-regulate LPS-induced expression of IL-1ß, in U-937 cells without a detectable effect upon the bioavailability of the cytokine. In similar culture conditions, MLIF was capable to down-regulate baseline and LPS-induced expression of IL-ß only in PBMC from patients with RA. Peptide effect on immunoreactivity of IL-1ß was not statistically significant. CONCLUSIONS: MLIF exerts, in primed cells, exquisite anti-inflammatory properties that deserve to be explored mechanistically.

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BACKGROUND: Neonatal sepsis is a worldwide public health issue in which, depending on the studied population, marked variations concerning its risk and prognostic factors have been reported. The aim of this study was to assess risk and prognostic factors for neonatal sepsis prevailing at a medical unit in southeastern Mexico. Thus, we used a historic cohort design to assess the association between a series of neonates and their mothers, in addition to hospital evolution features and the risk and prognosis of neonatal sepsis (defined by Pediatric Sepsis Consensus [PSC] criteria) in 11,790 newborns consecutively admitted to a Neonatology Service in Mérida, Mexico, between 2004 and 2007. RESULTS: Sepsis was found in 514 of 11,790 (4.3 %) newborns; 387 of these cases were categorized as early-onset (<72 h) (75.3 %) and 127, as late-onset (>72 h) (24.7 %). After logistic regression, risk factors for sepsis included the following: low birth weight; prematurity; abnormal amniotic fluid; premature membrane rupture (PMR) at >24 h; respiratory complications, and the requirement of assisted ventilation, O(2) Inspiration fraction (IF) >60 %, or a surgical procedure. Some of these factors were differentially associated with early- or late-onset neonatal sepsis. The overall mortality rate of sepsis was 9.5 %. A marked difference in the mortality rate was found between early- and late-onset sepsis (p >0.0001). After Cox analysis, factors associated with mortality in newborns with sepsis comprised the following: prematurity; low birth weight; low Apgar score; perinatal asphyxia, and the requirement of any invasive medical or surgical procedure. CONCLUSIONS: The incidence of neonatal sepsis in southeastern Mexico was 4.3 %. A different risk and prognostic profile between early- and late-onset neonatal sepsis was found.

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During carcinogenesis it is known that growth factors and cytokines from stromal and inflammatory cells from the microenvironment promote angiogenesis and lymphangiogenesis. However, the participation of macrophages and mast cells in these processes is not well understood. The aim of this study was to evaluate the relationship between mast cell and macrophage density with blood and lymphatic vessels in various stages of carcinoma of the uterine cervix. Tissue sections from archival paraffin-embedded samples from cases with cervical intraepithelial neoplasias (CIN) 1, 2, 3, carcinoma in situ, and invasive carcinoma were used. Immunohistochemical staining was done using the following antibodies: anti-LYVE-1; anti-CD31; anti-CD68, and anti-tryptase. Our results showed a significant increase in the number of macrophages in carcinoma in situ, a correlation between lymphatic vessels and macrophages in premalignant lesions CIN 2, and a correlation between mast cells and blood vessels in both CIN 2 and carcinoma in situ. In conclusion, our data underscore the importance of the recruitment of macrophages and mast cells in the development of tumor-associated blood and lymphatic capillaries.

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OBJECTIVE AND DESIGN: Monocyte locomotion inhibitory factor (MLIF), an amebic peptide with antiinflammatory properties, was evaluated in collagen-induced arthritis (CIA) to test its effects on the onset and acute inflammatory response of arthritis. MATERIAL: DBA1/J mice at 8-10 weeks of age were divided into four groups (eight mice per group). TREATMENT: The adjuvant group received Freund adjuvant, the CIA group was immunized with collagen II, the MLIF/CIA group received collagen II and MLIF, and the MLIF group received MLIF and Freund adjuvant. METHODS: All groups were evaluated clinically. Seven weeks after the collagen injection, at the peak of the clinical arthritis score, limb specimens were collected and histological studies and gene expression analysis using microarrays were performed. RESULTS: MLIF administered weekly as a preventive scheme delayed and reduced the severity of acute arthritis. MLIF induced gene changes in functional categories including adhesion molecules, matrix metalloproteinases, and inflammatory cytokines. CONCLUSIONS: MLIF could be an interesting new molecule to investigate in the field of rheumatoid arthritis pathogenesis research for its potential to prevent inflammation.

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