Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological effects of staphylococcal enterotoxins (SE), potentiated by bacterial lipopolysaccharide (LPS), were studied with mice. Control animals survived the maximum dose of either SE or LPS, while mice receiving both agents died. SEA was 43-fold more potent than SEB and 20-fold more potent than SEC1. The mechanism of toxicity was further examined with transgenic mice deficient in major histocompatibility complex class I or II expression. Class II-deficient mice were resistant to SEA or SEB. However, class I-deficient animals were less susceptible to SEA (30% lethality) than wild-type mice (93% lethality). In vitro stimulation of T cells from the three mouse phenotypes by SEA correlated well with toxicity. T cells from transgenic or wild-type mice were similarly responsive to SEA when presented by irradiated, wild-type mononuclear cells. These data confirmed that the toxicity of SE was mainly exerted through a mechanism dependent on the expression of major histocompatibility complex class II molecules. Toxicity was also linked to stimulated cytokine release. Levels in serum of tumor necrosis factor alpha, interleukin-6, and gamma interferon peaked 2 to 4 h after the potentiating dose of LPS but returned to normal within 10 h. Concentrations of interleukin-1 alpha were also maximal after 2 h but remained above the background for up to 22 h. Relative to the levels in mice given only SEA or LPS, the levels in serum of tumor necrosis factor alpha, interleukin-6, and gamma interferon increased 5-, 10-, and 15-fold, respectively, after injections of SEA plus LPS. There was only an additive effect of SEA and LPS on interleukin-1 alpha concentrations.
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PMID:Toxicity of staphylococcal enterotoxins potentiated by lipopolysaccharide: major histocompatibility complex class II molecule dependency and cytokine release. 822 6

It has been recently hypothesized that superantigens, which stimulate T cells expressing particular T cell receptor Vbeta chain gene segments, play a precipitating or aggravating role in psoriasis. In this study, we investigated the peripheral blood mononuclear cell (PBMC) response of patients with psoriasis vulgaris to staphylococcal superantigens (staphylococcal enterotoxin A (SEA), SEB, and SEC1) and its relationship to clinical and laboratory findings. Cytokine secretion was assessed by ELISA in the supernatants of the cultured PBMCs stimulated with SEB. Results of 3H-TdR uptake showed that the PBMCs' response against SEB in patients with psoriasis vulgaris (34,468 +/- 6,455) (mean DPM SD) was significantly higher than that of normal subjects (22,756 +/- 5,780) (p < 0.005). The stimulation index (SI) of patients with psoriasis vulgaris (n = 37) (63.9 +/- 55) was significantly higher than that of normal subjects (n = 24) (26.0 +/- 23) (p < 0.005) and patients with atopic dermatitis (n = 10) (40.7 +/- 30) (p < 0.05). Similar results were obtained in response to SEA and SEC1. SI weakly correlated with the psoriasis area and severity index (PASI) score (r = 0.62) and the serum interleukin-6 (IL-6) concentration (r = 0.45). IL-2 and tumor necrosis factor (TNF-alpha) were secreted at a significantly increased level by PBMCs from psoriatic patients on incubation with SEB, after a 3 day culture period. A higher level of IL-6 was released by PBMCs stimulated with SEB in psoriatic patients than normal controls, however, the difference was not significant. These results raise the possibility that monocytes, as well as T cells, are markedly activated by staphylococcal superantigen in patients with psoriasis vulgaris, which may play a role in the triggering or aggravating of psoriasis mediated by secreted cytokines.
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PMID:Clinical analysis of staphylococcal superantigen hyper-reactive patients with psoriasis vulgaris. 968 64