Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.
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PMID:[POEMS syndrome: role and value of interleukin-6]. 878 86

Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure. Although interferon gamma (IFN-gamma) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response. To examine the role of IFN-gamma in lipopolysaccharide (LPS)-induced injury, we administered LPS (20 or 800 microg/mouse) alone or as low-dose LPS (20 microg/mouse) 7 days after heat-killed Propionibacterium acnes (P. acnes) injection into wild-type C57BL/6 (B6) mice or IFN-gamma-deficient (GKO) mice (B6 background). Although low-dose (20 microg) LPS alone had no effect on survival, the administration of 800 microg LPS alone resulted in 100% mortality in both B6 and GKO mice without significant hepatic mononuclear cellular infiltration or differences in elevated plasma tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-12 levels. In contrast, mortality after low-dose (20 microg) LPS challenge in P. acnes-primed B6 mice was 100%, but 0% in GKO mice. In vivo plasma cytokine (IFN-gamma, TNF-alpha, IL-6, and IL-12) levels and in vitro cytokine production by hepatic mononuclear cells were significantly higher in B6 mice compared with GKO mice. Associated hepatic mononuclear cellular infiltration, multifocal liver necrosis, hepatomegaly, and splenomegaly were found in B6 mice, but not in GKO mice. Finally, the anti-inflammatory NK1.1+CD4+ cell proportion of hepatic infiltrating mononuclear cell numbers 7 days after P. acnes administration was significantly reduced in B6 compared with GKO mice, whereas the proportion of inflammatory NK1.1+CD4- cells was increased. In conclusion, these data suggest that IFN-gamma mediates P. acnes-primed low-dose LPS injury through the hepatic infiltration of mononuclear cells and the subsequent elevation of inflammatory cytokines after LPS challenge, whereas the lethal effects of high-dose LPS alone does not depend on the presence of IFN-gamma.
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PMID:The resistance of P. acnes--primed interferon gamma-deficient mice to low-dose lipopolysaccharide-induced acute liver injury. 1191 26

The multifunctional cytokine interleukin 6 (IL-6) is expressed in a wide variety of disease states and pathologic processes. Mice deficient in IL-6 display abnormal and delayed liver regeneration and repair. Currently, IL-6 is thought to influence liver growth indirectly by priming hepatocytes to respond to growth factors such as hepatocyte growth factor (HGF) by inducing expression of HGF and by inhibiting hepatocyte apoptosis, as distinct from the direct mitotic effects of IL-6 on myeloid and other cell types. Here, we show that systemic administration of IL-6 using CHO cell tumors in nude mice results in dramatic hepatomegaly and hepatocyte hyperplasia in the absence of liver injury. Liver mass and liver to body mass ratios increased to 2 to 3 times normal because of proliferation of hepatocytes. Liver growth was associated with high levels of serum IL-6 and with activation of the IL-6-signaling pathway, including increased expression of IL-6 receptor-alpha/gp80, activation of the signal transducer and activator of transcription-3 (STAT-3), and mitogen-activated protein kinase (MAPK/ERK)-signaling pathways and induction of downstream target genes, including c-myc. HGF receptor and transforming growth factor alpha (TGF-alpha)/epidermal growth factor (EGF) receptor activation were decreased in hypertrophied livers, suggesting that IL-6-induced liver growth was independent of these known hepatocyte mitotic pathways. In conclusion, we suggest that IL-6 may function as a direct hepatic mitogen in vivo and, furthermore, that IL-6 warrants closer examination as a potent liver growth factor with potential clinical utility for increasing liver mass following injury.
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PMID:Massive liver growth in mice induced by systemic interleukin 6 administration. 1288 76

Malignant mesothelioma is a rare aggressive solid tumor that is invariably incurable. A 23-year-old female patient with ascites, anemia, and high levels of ferritin and CRP was diagnosed with pleural mesothelioma by exploratory laparotomy. She remained asymptomatic, but 7 years later, she developed intractable diarrhea and fever. Systematic chemotherapy with both cisplatin and pemetrexed was administered. However, the treatment was discontinued due to side effects, after which time the diarrhea, ascites, and fever became progressively more severe. Hepatomegaly and hepatic siderosis also developed. At the same time, the patient's serum interleukin 6(IL-6)levels were abnormally high. Although there was a temporary symptomatic improvement after intraperitoneal injection of cisplatin, the intractable mesothelioma-associated symptoms returned a few days later. The patient died of liver failure 1 week later. The poor prognosis in this case was due to symptoms associated with the high IL-6 level. There are limited medically proven treatments, and it is important to develop new treatments. Therefore, "anti-IL-6 therapy" may have to be tested as a potential treatment for symptoms associated with high IL-6 levels.
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PMID:[Malignant Pleural Mesothelioma with Excessive Inflammation and High Level of Interleukin 6 - A Case Report]. 2813 37