Level Of Amyloid Research Articles

Augmentation of Type I IL-1 Receptor Expression and IL-1 Signaling by IL-6 and Glucocorticoid in Murine Hepatocytes

AbstractIL-1 signal is transduced through type I receptor (IL-1RI). We have recently reported that LPS augments IL-1RI mRNA expression in the hepatocytes of mice in vivo, and the augmentation is mediated by the interaction of IL-1, IL-6, and glucocorticoid (GC). In this study, we examined whether IL-1RI mRNA expression level in the hepatocytes reflects those of cell surface molecule and IL-1 signaling. When primary cultured murine hepatocytes were treated with dexamethasone (Dex) or IL-6, these two reagents synergistically up-regulated IL-1RI mRNA expression in the cells. 125I-labeled IL-1 binding experiment showed that the level of binding was also up-regulated by the treatment with Dex and IL-6. Scatchard analysis revealed that the number of IL-1R increased. The increased binding of IL-1 was completely inhibited by an Ab against murine IL-1RI, indicating that Dex and IL-6 augmented the expression of cell surface IL-1RI molecule. When hepatocytes were pretreated with Dex and IL-6, the activation of IL-1R-associated kinase was augmented in response to IL-1, indicating that IL-1 signaling was also augmented. In addition, IL-1 treatment following administration of the combination of Dex and IL-6 into mice markedly increased the serum level of serum amyloid A. These results indicate that GC and IL-6 augment the expression of cell surface IL-1RI in hepatocytes, as well as IL-1 signaling and IL-1R-associated kinase activation, through up-regulation of IL-1RI mRNA level, which represents a novel regulatory network between IL-1, GC, and IL-6.

Salazosulfapyridine(SASP)投与が有効であった慢性間接リウマチに伴う続発性アミロイド腎症の1例

A 55-year old female with rheumatoid arthritis (RA) had presented with proteinuria since July 1996. She was referred to us for persistent edema on her face and legs in November 1996. On admission, her 24-hour urinary protein excretion was 4.4 g/day, total serum protein level was 5.3 g/dl, and serum level of amyloid A protein (SAA) was elevated to 45.8 mg/ml. A percutaneous renal biopsy was performed, and light microscopy revealed varying degrees of amyloid deposits in the mesangial areas and arteriolar walls. The diagnosis of secondary amyloidosis (AA amyloidosis) was based on immunohistochemical staining for amyloid A protein using monoclonal antibody against SAA. Four weeks after treatment with salazosulfapyridine (SASP) and dipyridamole, proteinuria began to decrease and the edema had disappeared. Finally she recovered from nephrotic syndrome. AA amyloidosis has been thought to have a poor prognosis, with progression to renal failure. Since there is no specific effective therapy for the disease, it is very important to reduce the activity of the underlying cause. In our patient with renal amyloidosis following RA, SASP was evidently effective for arthritis and improvement of renal function. SASP might have a beneficial effect on AA amyloidosis by suppressing inflammatory cytokines.

Unstable Angina: Are We Able to Recognize High-Risk Patients?

It is difficult to identify characteristics of patients with unstable angina that are predictive of a high likelihood of developing clinical events. However, several features have been recognized. Patients with a clinical history of previous stable exertional angina symptoms who began to experience rest pain appear to be at risk and tend to have more extensively underlying coronary disease. When the ischemic episodes are accompanied by rates, a new or worsening mitral regurgitation murmur, or hypotension, there is a high likelihood of significant coronary artery disease and one should triage these patients to early cardiac catheterization and prompt revascularization. An angiographic feature that carries a high risk is a lesion in the proximal left anterior descending or in the left main coronary artery. Certain typical ECG patterns are very suggestive for a critical narrowing in these coronary arteries. If chest pain and ST-segment changes recur on vigorous medical management, early invasive evaluation should be strongly considered. Even so, the left ventricular function is very important prognostically. According to serologic tests, the level of C-reactive protein and serum amyloid A protein suggesting that there may be active inflammation predicts an early poor outcome. However, these serologic abnormalities do not have much clinical value. An increased platelet activation and a reduced fibrinolytic capacity play a role in the pathogenesis of unstable angina, but thrombolytic therapy does not improve the prognosis in patients with unstable angina.

Serum Amyloid A to Monitor Cancer Dissemination

The level of serum amyloid A, a protein previously found to behave as an acute-phase reactant, was measured by a radioimmunoassay in 621 patients with various neoplastic diseases free of inflammatory processes. In all but eight of the 289 patients with solid tumors with distant metastases, in all patients with myelocytic leukemia with high leukocyte counts, and in all patients with advanced lymphoma, the serum amyloid A level was above 400 ng/mL. It was below this value in all tested patients with lymphocytic leukemia and in 250 of 270 patients with solid malignant tumors with localized or regional disease. Among the 20 patients from this latter group with levels higher than 400 ng/mL, 16 developed distant metastases within 214 days from the initial measurement. The serum amyloid A level decreased significantly in patients with lymphoma and those with metastatic solid tumors who responded to chemotherapy. Thus the level of serum amyloid A can be used as a biochemical marker that discriminates between disseminated and localized or regional disease, and monitors the response to therapy.

Lymphoid cells in endotoxin-induced production of the amyloid-related serum amyloid A protein

Endotoxin-treated mice exhibit a rapid rise in the level of the serum amyloid A (SAA) protein, but this effect is not observed in endotoxin-resistant C3H/HeJ mice. To evaluate the role of lymphoid cells in the production of SAA protein, C3H/HeJ mice were adoptively transfused with endotoxin-sensitive (C3H/HeN) bone marrow cells. After such adoptive transfer, endotoxin treatment of C3H/HeJ mice resulted in high serum levels of SAA protein. The ability of chimeric mice to make SAA protein correlated with the presence of endotoxin-sensitive B lymphocytes and macrophages. These findings suggest that lymphocytes and/or macrophages play an important role in initiating SAA protein synthesis after endotoxin treatment and suggest a possible mechanism by which chronic infection or inflammation leads to amyloidosis.