Bacterial endocarditis due to corynebacterium. Report of 2 cases.
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Anti-Bacterial Agents↗
Biomedical subjects
W Falk
Publications and source records attributed to W Falk.
Tumor necrosis factor: a cytokine involved in toxic effects of endotoxin.
Endotoxin-induced tumor necrosis has been shown to be mediated by a factor termed tumor necrosis factor (TNF). The biochemical nature, source, and mode of induction of TNF have been clarified. TNF is a mediator of activated macrophages that is released into the supernatant by these cells after their stimulation with endotoxin. A number of biologic functions of TNF other than its tumoricidal activity have been demonstrated. In vivo, TNF induces reactions similar to those induced by endotoxin. Hypothermia, elevated hematocrit and plasma lactate levels, and reduced plasma glucose levels have been measured in mice injected with TNF. These reactions typically occur soon after endotoxin injection and are induced with purified recombinant TNF in mice that exhibit a low response to endotoxin. No TNF-induced production of interleukin 1 (which can induce similar effects) was detected in macrophage/monocyte cultures. Therefore, TNF appears to mediate endotoxin effects directly.
Animals↗
Autocrine growth factors secreted by the malignant human B-cell-line BJAB are distinct from other known cytokines.
BJAB, a EBV-negative Burkitt-like lymphoma, did not grow under suboptimal culture conditions in low concentrations of serum unless appropriate cytokines were added. A subclone of BJAB, Clone 13, however, could be kept in long-term culture under such conditions without added cytokines. This suggested that growth of BJAB-Clone 13 was supported by autocrine growth factors (AGF). In fact, the supernatant of Clone 13 stimulated growth of the parental BJAB line and showed IL-1-like activity. Of several cytokines tested only AGF and IL-1 stimulated growth of BJAB. IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, GM-CSF, TNF-alpha, LT, IFN-gamma and TGF beta did not have this effect. The IL-1-like activity was completely neutralized by anti-IL-1 alpha antibodies. In contrast, AGF-activity was not affected by anti-IL-1 alpha. Rabbit antibodies produced against fractions enriched for AGF inhibited growth of BJAB. This inhibition was overcome by Clone 13-AGF, but not by IL-1 alpha. These data suggest that Clone 13-AGF is distinct from IL-1 alpha and might be a new cytokine.
Antibodies↗
The internalized interleukin-1 activation complex in fibroblasts localizes to the Golgi apparatus.
In order to investigate binding and internalization of interleukin-1 (IL-1) by confocal laser scanning microscopy, we established a model system comprising an IL-1 receptor type I (IL-1R1) overexpressing transfectant of the murine fibrosarcoma cell line L929 (L929R1) and an N-terminal FLAG-tagged human recombinant IL-1 alpha (FLAG-IL-1 alpha). The function of the transfected receptors was shown by their IL-1-induced association with a kinase activity. The biological activity of the purified FLAG-IL-1 alpha was comparable to the unmodified molecule. L929RI cells were exposed to saturating concentrations of FLAG-IL-1 alpha. Two-color fluorescence analysis revealed increasing cell surface binding of FLAG-IL-1 alpha to the receptor over 30 min. This was followed by internalization and accumulation of the ligand/receptor complex at the Golgi apparatus. After 3 hr the receptor signal significantly decreased and patches of FLAG-epitopes reappeared on the cell surface, no longer colocalized with IL-1R1. Thus, in this model, the previously assumed nuclear accumulation of IL-1 was not detected but rather localization of the internalized IL-1/IL-1R1-complex to the Golgi apparatus was found. Direct effects of IL-1 on the nucleus or the nuclear membrane therefore are unlikely.
Animals↗
Evidence for an intracellular activation loop in the IL-1 system.
The mechanism of action of the pleiotropic cytokine interleukin-1 (IL-1) is only incompletely understood. A unique feature among cytokines is its internalization and translocation to the nuclear area in nondegraded form, suggesting intracellular activities of the molecule. To define activities of that kind, a pair of IL-1 receptor type I (IL-1RI)-positive EL4 thymoma cells with differential receptor functionality was transfected with plasmids which caused intracellular expression of FLAGIL-1 alpha fusion peptides. Intracellular delivery of IL-1 costimulated expression of IL-2 mRNA and production of IL-2 protein. This effect was not mediated by the plasma membrane IL-1RI. The cells were permanently activated, and in cells with functional IL-1RI, appearance of membrane IL-1RI was abrogated. Thus, intracellularly delivered IL-1 can bypass and replace the plasma membrane IL-1RI, possibly via an as yet undefined intracellular receptor. This is a new modality of IL-1 action and suggests a role for the intracellular IL-1R antagonists (icIL-IRa).
Cell Membrane↗