Biomedical subjects

Rogier J L Stuyt

Publications and source records attributed to Rogier J L Stuyt.

6 recordsLinked to original sources

PubMed2005

Interleukin-18 does not modulate the acute-phase response.

IL-18 is a pro-inflammatory cytokine of the IL-1 family and it induces IL-1, TNF, and IL-6, all of which are endogenous pyrogens. The pyrogenic properties of recombinant IL-18 were studied in a rabbit model of fever. rIL-18 did not cause fever when injected intravenously into rabbits. Furthermore, the ability of rIL-18 to modulate other components of the acute-phase response was assessed. rIL-18 did not induce leukocytosis, or changes of circulating concentrations of lipoproteins and corticosterone in mice. In conclusion, rIL-18 is not able to induce a febrile response in rabbits and does not modulate the acute-phase response in mice.

Acute-Phase Reaction↗

PubMed2004

Recombinant interleukin-18 protects against disseminated Candida albicans infection in mice.

Endogenous interleukin (IL)-18 is necessary for host defense against candidiasis. Prophylactic treatment of Candida albicans-infected mice with recombinant murine (r) IL-18 decreased mortality, which was accompanied by a decreased outgrowth of yeasts in the kidneys 1 day after infection. Therapeutic administration of rIL-18 also resulted in decreased outgrowth of C. albicans in the kidneys and increased levels of interferon- gamma, both in the circulation and after in vitro stimulation of splenocytes with C. albicans. Histopathologic analysis of the kidneys showed increased inflammation and decreased growth of C. albicans in rIL-18-treated mice. In conclusion, rIL-18 improves outcome of disseminated candidiasis in mice and may prove useful as adjuvant immunotherapy of fungal infections.

Animals↗

PubMed2003

Regulation of Staphylococcus epidermidis-induced IFN-gamma in whole human blood: the role of endogenous IL-18, IL-12, IL-1, and TNF.

Interleukin 12 (IL-12) and IL-18 act synergistically to stimulate interferon gamma (IFN-gamma) production; moreover, IL-1 and tumor necrosis factor (TNF) may also augment IFN-gamma synthesis. We have investigated the relative contributions of these cytokines in the production of IFN-gamma and TNF by the Gram-positive bacterium Staphylococcus epidermidis, using the specific cytokine inhibitors IL-18 binding protein (IL-18BP), IL-1 receptor antagonist (IL-1Ra), anti-IL-12 antibodies (anti-IL-12 Ab), and TNF binding protein. Inhibition of caspase-1 reduced IFN-gamma and IL-1beta levels (by 80 and 67%, respectively) when heat-killed S. epidermidis was added to whole human blood cultures. IL-18BP reduced S. epidermidis-induced IFN-gamma (77% maximal suppression). In contrast, blocking IL-1 receptors by IL-1Ra had no effect on IFN-gamma production. Blocking endogenous IL-12 and TNF reduced IFN-gamma production by 69 and 36%. S. epidermidis-induced TNF-alpha was inhibited by IL-18BP and IL-1Ra, but not anti-IL-12 Ab, whereas IL-8 production was unaffected by any of the specific cytokine blocking agents. In conclusion, S. epidermidis stimulates IFN-gamma which is IL-18, IL-12 and TNF-dependent, but IL-1 independent.

Adult↗

PubMed2003

Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes.

Induction of expression of adhesion molecules is a crucial step in inflammation. The role of interleukin-18 (IL-18) in induction of various adhesion molecules was investigated in freshly isolated peripheral blood mononuclear cells and human monocyte and T-cell lines. IL-18 selectively up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on freshly isolated human monocytes, but not on lymphocytes. The expression of other adhesion molecules was not influenced. Induction of ICAM-1 by IL-18 was dependent on endogenous tumour necrosis factor-alpha (TNF-alpha), and IL-12 had an additive effect on that of IL-18. No changes in adhesion molecule expression were observed on the monocytic cell line THP-1 and on the T-cell lines HSB-2 and Jurkat J16. In addition, induction of ICAM-1 on monocytes by lipopolysaccharide was slightly, but significantly, inhibited by blockade of either endogenous IL-18 or TNF-alpha with IL-18 binding protein or TNF binding protein, respectively. Blocking IL-1 effects with IL-1 receptor antagonist did not influence ICAM-1 levels. In conclusion, IL-18 selectively up-regulates the expression of ICAM-1 on monocytes, and this contributes to the proinflammatory effects of this cytokine.

Cell Adhesion Molecules↗

PubMed2002

The role of endogenous interleukin (IL)-18, IL-12, IL-1beta, and tumor necrosis factor-alpha in the production of interferon-gamma induced by Candida albicans in human whole-blood cultures.

Despite the importance of interferon (IFN)-gamma, tumor necrosis factor (TNF), and interleukin (IL)-18 for host defense against candidiasis, the pathways leading to their stimulation by Candida albicans are unclear. In a whole-blood model, IL-18 neutralization by IL-18 binding protein decreased C. albicans-induced IFN-gamma synthesis by 72%. Similarly, neutralization of IL-12 or IL-1beta by either neutralizing antibodies or IL-1 receptor antagonist also reduced (by 65%) IFN-gamma production. Neutralization of TNF by TNF binding proteins resulted in only a 36% reduction of IFN-gamma synthesis. In contrast, production of TNF and IL-8 was largely unaffected by these cytokine inhibitors. Thus, C. albicans stimulates IFN-gamma production in an IL-18-, IL-12-, and IL-1beta-dependent manner, whereas production of TNF and IL-8 is independent of these cytokines. Blocking the biologic activities of IL-18, IL-12, and IL-1beta in patients (e.g., for treatment of autoimmune diseases) may result in increased susceptibility to C. albicans infection.

Adult↗

PubMed2002

Role of interleukin-18 in host defense against disseminated Candida albicans infection.

In mice injected intravenously with Candida albicans, administration of anti-interleukin-18 (IL-18) antibodies increased the yeast load in the kidneys. There was no effect on the organ load with Candida when gamma interferon (IFN-gamma)-deficient mice were treated with anti-IL-18 antibodies, suggesting that the protective effect of IL-18 is mediated through endogenous IFN-gamma.

Animals↗