Correlation of Interleukin-6 Gene Expression to Immunologic Features in Patients with Cardiac Myxomas

Abstract

Cardiac myxomas, the most common primary heart tumors in adults, show a variety of clinical manifestations and laboratory findings correlated with elevated interleukin-6 (IL-6) serum concentration. The aim of this study was to determine the expression of IL-6 mRNA in myxoma tissue as a cause to frequent immunologic abnormalities in patients with such tumors. In our centers, we analyzed 17 surgically resected myxomas using the polymerase chain reaction (PCR) and found increased IL-6 mRNA expression in 14 of 17 cases. The serum IL-6 levels of the 14 patients, detected by enzyme-linked immunosorbent assay (ELISA) with mouse antihuman monoclonal antibody (mAb), were high preoperatively (> 6 pg/ml) and decreased to normal postoperatively (< or = 6 pg/ml). These same 14 patients exhibited significant autoimmune disorders preoperatively. The other 3 patients had normal serum levels of IL-6 (< or = 6 pg/ml) and did not present any serious signs and symptoms, and molecular analysis did not show overexpression of IL-6 mRNA in neoplasmic tissue. These results suggest that IL-6 is overproduced in myxoma tissue and secreted into the systemic circulation as a stimulator of the immunoregulatory system. Furthermore, this study indicates the promising role of molecular biology techniques in the research of pathophysiologic mechanisms of cardiac myxomas.

Cardiac Myxomas: A 50-Year Experience With Resection and Analysis of Risk Factors for Recurrence

“…Size ranges from 2 to 3 mm to 15 cm and can weigh as much as 450 g. Microscopically, the myxoma is composed of stellate, fusiform, or plump cells and cytologically bland mesenchymal cells in a myxoid stroma. The cells are arranged singly, in cords, or in the form of rings [9][10][11]. In our series, myxomas had a higher preponderance in female patients.…”

Multiple Fusiform Cerebral Aneurysms and Highly Elevated Serum Interleukin-6 in Cardiac Myxoma

“…The IL-6 was highly expressed in the myxomatous cells in an immunohistochemical study 3) . Serum IL-6 level is usually elevated in patients with CM, and is normalized immediately after surgical removal of CM 5) . Mendoza,et al 3) demonstrated that there was a posi- tive correlation between serum IL-6 level and size of CM, and that overproduction of IL-6 by myxomatous cell was associated with tumor recurrence or distal embolization 3) .…”

Increased Expression and Activity of Matrix Metalloproteinases Characterize Embolic Cardiac Myxomas

“…It has been previously reported that embolic myxomas constitutively express high levels of IL-6. 9 Autocrine production of IL-6 may represent one of the mechanisms responsible for the excessive MMP synthesis in embolic myxomas. Increased MMP delivery in the medium of embolic myxoma cultures also suggests that the increase of MMP plasma levels may represent an additional peripheral marker to identify patients at risk of embolism among those cases in which echocardiographic criteria are not characteristic.…”

“…[1][2][3][4][5]8 Because most myxomas are left atrium-located, emboli prevalently involve peripheral districts, in particular cerebral arteries, including the retinal artery. [1][2][3]8 Echocardiographic polypoid and irregular macroscopic aspects, 3,5 changes in the composition of the myxomatous matrix, 6 as well as the autocrine production of interleukin (IL)-6 9 have been considered, but the real causes of embolism in cardiac myxomas are still unknown. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes that are responsible for ECM remodeling in both normal and pathological processes.…”