Serum levels of interleukin-6 in multiple myeloma and other hematological disorders: correlation with disease activity and other prognostic parameters.
Interleukin-6 (IL-6) is a multifunctional cytokine involved in the regulation of the terminal differentiation pathway of B lymphocytes. Recent reports revealed its potential role in the in vitro and in vivo growth of human multiple myeloma cells. The mechanism, however, by which IL-6 triggers proliferation of malignant plasma cells remains controversial. Using the very sensitive 7TD 1 bioassay we quantified endogenous circulating IL-6 levels in serum samples of 104 patients suffering from monoclonal gammopathies and other hematological disorders [47 with multiple myeloma (MM), 24 with monoclonal gammopathy of unknown significance (MGUS), 8 with myeloproliferative disease, and 25 suffering from low-grade non-Hodgkin's lymphoma (NHL)]. Elevated serum levels of IL-6 (greater than 5 pg/ml) were detected in 42% of the patients with MM, in 13% with MGUS, in 15% with low-grade B-NHL, and in 1 patient with T-NHL. In patients suffering from chronic myeloproliferative diseases, IL-6 levels were within the normal range. In patients with myeloma, IL-6 levels were significantly higher at advanced stages (II/III) or with progressive disease than in patients with MM stage I, MGUS, or at the plateau phase (P less than 0.01). In patients with monoclonal gammopathies including MGUS, serum IL-6 levels correlated with neopterin, tumor necrosis factor alpha and beta 2-microglobulin. An inverse correlation was found with hemoglobin levels. From these results, we propose that in myeloma patients serum IL-6 levels may reflect disease activity and tumor cell mass. The correlation with serum neopterin, a macrophage product, also suggests its origin in an activated immune system.
Nachbaur
D M
DM
University Hospital of Internal Medicine, Department of Oncology and Immunohaematology, Innsbruck, Austria.
Herold
M
M
Maneschg
A
A
Huber
H
H
D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D006402:Hematologic Diseases / Q000097:blood*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood; D009101:Multiple Myeloma / Q000097:blood*; D009196:Myeloproliferative Disorders / Q000097:blood; D019798:Neopterin; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin