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IL-18 Production (il-18 + production)

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Medical Sciences	75%

Selected Abstracts

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2003
TAKAHIRO ISHIKURA
Abstract Background and Aim:, The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. Methods:, Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. Results:, The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. Conclusions:, These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice. [source]

Monocyte cytokine and costimulatory molecule expression in patients infected with Leishmania mexicana

PARASITE IMMUNOLOGY, Issue 3 2007
G. CARRADA
SUMMARY Leishmania mexicana causes localized and diffuse cutaneous leishmaniasis. Patients with localized cutaneous leishmaniasis (LCL) develop a benign disease, whereas patients with diffuse cutaneous leishmaniasis (DCL) suffer from a progressive disease associated with anergy of the cellular response towards Leishmania antigens. We evaluated the production of the interleukins (IL) IL-12, IL-15, IL-18 and tumour necrosis factor-, (TNF-,) and the expression of the costimulatory molecules CD40, B7-1 and B7-2 in monocytes from LCL and DCL patients, stimulated in vitro with Leishmania mexicana lipophosphoglycan (LPG) for 18 h. LCL monocytes significantly increased TNF-,, IL-15 and IL-18 production, and this increase was associated with reduced amounts of IL-12. DCL monocytes produced no IL-15 or IL-18 and showed a decreasing tendency of TNF-, and IL-12 production as the severity of the disease increased. No difference was observed in the expression of CD40 and B7-1 between both groups of patients, yet B7-2 expression was significantly augmented in DCL patients. It remains to be established if this elevated B7-2 expression in DCL patients is cause or consequence of the Th2-type immune response that characterizes these patients. These data suggest that the diminished ability of the monocytes from DCL patients to produce cell-activating innate proinflammatory cytokines when stimulated with LPG is a possible cause for disease progression. [source]

Blocking ERK-1/2 reduces tumor necrosis factor ,,induced interleukin-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin-18 binding protein A

ARTHRITIS & RHEUMATISM, Issue 3 2010
Hubert Marotte
Objective To examine the mechanism of regulation of interleukin-18 (IL-18) bioactivity by IL-18 binding protein (IL-18BP) induction. Methods Levels of IL-18 and IL-18BPa in synovial fluid samples from patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were determined by enzyme-linked immunosorbent assays (ELISAs), followed by calculation of free IL-18. IL-18 and IL-18BPa synthesis in RA synovial fibroblasts that had been treated with proinflammatory and antiinflammatory cytokines were assessed by quantitative real-time polymerase chain reaction and ELISA, respectively, followed by IL-18 bioactivity determination using KG-1 cells. Chemical signaling inhibitors were used for determination of the signal transduction pathways involved in IL-18BPa/IL-18 regulation. Tumor necrosis factor , (TNF,),induced caspase 1 activity was determined by a colorimetric assay. Results IL-18BPa was lower in RA synovial fluid than in OA synovial fluid (P < 0.05; n = 8), and free IL-18 was higher in RA synovial fluid than in OA synovial fluid. TNF, induced RA synovial fibroblast IL-18BPa and IL-18 in a time-dependent manner (P < 0.05). Evaluation of signaling pathways suggested that TNF, induced IL-18 production through the ERK-1/2, protein kinase C, (PKC,), and Src pathways, whereas IL-18BPa synthesis was mediated through the NF,B, PKC, Src, and JNK pathways. Furthermore, addition of exogenous IL-18BPa-Fc reduced the RA synovial fibroblast phosphorylation of ERK-1/2 induced by TNF,. Conclusion These results suggest that IL-18BPa reduces IL-18 bioactivity induced by TNF,, by regulating the ERK-1/2 pathway in RA synovial fibroblasts. Targeting IL-18 bioactivity by induction or addition of IL-18BPa may provide another therapeutic option in the management of RA. [source]

Cytokine detection in HIV-1/HHV-8 co-infected subjects

CELL BIOCHEMISTRY AND FUNCTION, Issue 3 2002
Agostino Pugliese
Abstract In a previous work we have evaluated some immunologic and haematologic parameters of HIV-1 positive subjects co-infected with HHV-8. A worsening of these values were generally described in these patients as compared with those HIV-1 positive, but negative for HHV-8. Now we have studied the influence of HHV-8 co-infection of HIV-1 positive subjects on the production of some cytokines to make clear the question of its role in the immuno-deregulation of the above-mentioned subjects. In particular we have analysed serum levels of IL-4 and IL-10, Th2 type T cells cytokines, IFN-,, an indirect marker of Th1 cells activation and IL-18, a cytokine produced by monocytic-macrophagic cells, which is able to induce IFN-, production and Th1 T lymphocytes activation. No significant differences were found as regards the IFN-, serum levels (92.1,±,24.3 pg ml,1 in the case of HIV-1 positive/HHV-8 negative subjects and 96.0,±,17.4 pg ml,1 in those HIV-1 positive/HHV-8 positive). In healthy subjects the mean level of this cytokine was 17.6,±,5.2 pg ml,1 (significant difference with both the former values at p,<,0.001). Moreover IL-4 and IL-10, which were undetectable in healthy individuals, showed the following values in HIV-1positive/HHV-8 negative subjects: 31.9,±,2.7 pg ml,1 and 119.8,±,85.1 pg ml,1 respectively and in HIV-1 positive/HHV-8 positive subjects: 30.4,±,4.8 pg ml,1 and 69.4,±,65.3 pg ml,1 (not significant differences). In contrast IL-18 reached a mean level of 1001.2,±,360.5 pg ml,1 in HIV-1 positive/HHV-8 negative subjects, but showed a significant reduction in HIV-1 positive/HHV-8 positive subjects (737.6,±,284.3 pg ml,1,p,<,0.05) and presented very low levels in healthy individuals (21.3,±,30.3 pg ml,1). Moreover a significant correlation (,0.984,p,<,0.001) was noticed between IL-18 reduction in HIV-1 positive subjects co-infected with HHV-8 and the degree of positivity of HHV-8. These data suggest that HHV-8 co-infection has no influence on the switch Th1, Th2 in HIV-1 positive subjects, but is able to reduce IL-18 production, useful for Th1 subset restoration. Copyright © 2002 John Wiley & Sons, Ltd. [source]