scholarly journals Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 765-771 ◽  
Author(s):  
TT Pelliniemi ◽  
K Irjala ◽  
K Mattila ◽  
K Pulkki ◽  
A Rajamaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Regression Analysis ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Proteins ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Serum Levels ◽  
High Serum ◽  
Bone Lesions

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2- microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.

Acute Phase Proteins and Interleukin?6 Serum Levels in Patients with Chronic Arterial Occlusion

2006 ◽  
Vol 762 (1) ◽  
pp. 493-495 ◽  
Author(s):  
WACLAW MAJEWSKI ◽  
RYSZARD STANISZEWSKI ◽  
ARTUR SLUPIANEK ◽  
ALEKSANDER GORNY ◽  
ANDRZEJ MACKIEWICZ
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Proteins ◽  
Arterial Occlusion ◽  
Serum Levels ◽  
Chronic Arterial Occlusion

Influence of Renal Failure on the Osteoprotegerin Level in Patients with Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4999-4999
Author(s):  
Stefcho Goranov ◽  
Veselina Goranova-Marinova ◽  
Emil Kumchev ◽  
Pavel Pavlov ◽  
Todorka Tzvetkova
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Clinical Stage ◽  
Correlation Coefficients ◽  
Serum Levels ◽  
Function Parameter ◽  
Renal Diseases ◽  
Bone Lesions ◽  
Low Grade ◽  
Phase Dynamics

Abstract The aim of the study is to analyse the osteoprotegerin (OPG) level in patients with multiple myeloma (MM), primary renal diseases with renal failure (PRD with RF) and healthy controls and to assess the influence of RF on the correlations of OPG with basic parameters for MM. Serum levels of OPG (ELISA kits, Biomedica, Vienna) were studied in 66 newly diagnosed patients with MM, 51 with PRD and RF and 32 controls. In MM patients OPG is presented also as OPG/creatinin ratio and is studied acc to the clinical stage (Durie and Salmon), bone marrow infiltration, grade of myeloma bone disease (MBD) using the Merlini scale, b2-microglobulin and LDH. Statistics were done by SPSS v 11.0 (variative, alternative, correlative, non-parametric analyses, Mann-Whitney test, one-way ANOVA; at p<0,05). OPG levels in MM patients do not differ from PRD with RF group but are significantly higher compared with the controls (tabl.1). OPG/creatinin eliminates the difference between the MM patients and controls: 0,043±0,003 vs 0,037 ± 0,001, p>0,05. In patients with PRD OPG is significantly higher in II gr. RF (p<0,02) while in MM patients its level does not depend on the grade of RF. In I clinical stage OPG is significantly higher than in III stage (6,34 ± 0,724 vs 4,245 ±0,407 pmol/l, p<0,03). MM patients with RF have significantly higher OPG than these without RF. The proportion of MM patients with RF and elevated OPG >6,0pmol/l is about 2,5 times higher (68,7%) than the proportion of patients with low OPG<3,44pmol/l (25,0%), p<0,05. MM patients with minimal and no bone lesions+RF have significantly higher OPG than these with severe MBD + RF (9,97 ± 2,42 vs 4,92 ± 0,62 pmol/l, p<0,05). The correlations of OPG are stronger for OPG/creatinin and are most expressed in the MM group without RF. RF “masques” the clinical correlations of OPG (tabl.2). OPG levels in MM show phase dynamics: initial elevation in early clinical stages and low grade bone lesions (successful counteraction to intensive bone resorbtion) followed by decrease in the advanced stages and severe MBD. These data we explain with the combined but opposite effects of RF (elevates OPG providing skeletal resistance in uremia) and the specific, not-possible-to overcome action of myeloma tumor burden (directly degrades OPG and inhibits osteoblast function). OPG levels in patients with MM, PRD and controls Groups N OPG pmol/l mean±SEM P *vs controls Controls 32 3,77 ± 0,33 0,01 MM 66 5,36± 0,45 MM without RF 39 4,51 ± 0,30 0,001 MM with RF 27 6,60 ± 1,00 MM with I gr RF (cr 166–353 mol/l) μ 18 6,73 ± 1,37 NS MM with II gr RF (cr 353– 707 mol/l) μ 9 6,20 ± 1,32 PRD with RF 51 5,74± 0,36 0,001* PRD with I gr RF 23 4,50± 0,32 0.02 PRD with II gr RF 28 6,75± 0,51 Correlation coefficients of OPG in MM and eliminating the influence of renal function Parameter OPG pmol/l OPG/creatinin OPG pmol/l (without RF) p r p r p r Clinical stage <0,05 −0,275 <0,001 −0,616 <0,001 − 0,669 MBD <0,05 −0,323 <0,001 −0,521 <0,001 − 0,556 m. infiltration N.S. <0,001 −0,530 <0,001 − 0,562 ß2-microglobulin <0,05 +0,375 N.S N.S LDH N.S N.S <0,05 −0,338

scholarly journals Multiple myeloma presenting high fever and high serum levels of lactic dehydrogenase, CRP, and interleukin-6

2000 ◽  
Vol 64 (1) ◽  
pp. 76-77 ◽  
Author(s):  
Hirokazu Murakami ◽  
Satoru Takada ◽  
Nahoko Hatsumi ◽  
Akihiko Yokohama ◽  
Takayuki Saitoh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Interleukin 6 ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
High Serum ◽  
High Fever

scholarly journals Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1454
Author(s):  
Daniela Damasceno ◽  
Julia Almeida ◽  
Cristina Teodosio ◽  
Luzalba Sanoja-Flores ◽  
Andrea Mayado ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Serum Levels ◽  
Bone Alkaline Phosphatase ◽  
High Serum ◽  
Bone Lesions ◽  
Bone Homeostasis ◽  
Normal Bone ◽  
End Stage ◽  
Undetermined Significance

Background. Monocyte/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment. Methods: We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS (n = 23), SMM (n = 14) and MM (n = 99) patients vs. healthy donors (HD; n = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers. Results: Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM (p ≤ 0.02), in association with lower blood counts of recently-produced CD62L+ cMo in SMM (p = 0.004) and of all subsets of (CD62L+, CD62L− and FcεRI+) cMo in MM (p ≤ 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS (p ≤ 0.03), SMM (p ≤ 0.03) and MM (p ≤ 0.002), while normal (MGUS and SMM) or decreased (MM; p = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1β were observed in MGUS (p = 0.007) and SMM (p = 0.01), higher concentrations of serum IL8 were found in SMM (p = 0.01) and MM (p = 0.002), and higher serum IL6 (p = 0.002), RANKL (p = 0.01) and bone alkaline phosphatase (BALP) levels (p = 0.01) with decreased counts of FcεRI+ cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1β and/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly (p = 0.01) decreased blood counts of immunomodulatory FcεRI+ cMo-, typical of MM presenting with bone lesions. Conclusions: These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of FcεRI+ cMo in normal bone homeostasis.

Incidence of apoptosis and cell proliferation in multiple myeloma. Correlation with bcl-2 protein expression and serum levels of interleukin-6 (IL-6) and soluble IL-6 receptor

2002 ◽  
Vol 69 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Aristeidis I. Chaidos ◽  
Maria C. Bai ◽  
Sevasti A. Kamina ◽  
Panayiotis E. Kanavaros ◽  
Niki J. Agnantis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Interleukin 6 ◽  
Serum Levels

Synergistic action of interleukin-6 and glucocorticoids is mediated by the interleukin-6 response element of the rat alpha 2 macroglobulin gene

1992 ◽  
Vol 12 (5) ◽  
pp. 2282-2294
Author(s):  
G M Hocke ◽  
D Barry ◽  
G H Fey
Keyword(s):  
Dna Binding ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Binding Proteins ◽  
Nuclear Dna ◽  
Acute Phase Proteins ◽  
Dna Binding Proteins ◽  
Human Hepatoma Cells ◽  
Response Element ◽  
Multiple Copies

One class of genes coding for the acute-phase proteins (acute-phase genes) is induced by interleukin 6 (IL-6) through the human transcription factor NF-IL-6 and its rat homolog IL-6-DBP/LAP. A second class, represented by the rat alpha 2 macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) and different DNA-binding proteins interacting with this element, the so-called IL-6-RE binding proteins (IL-6 RE-BPs). Human Hep3B and HepG2 hepatoma, U266 myeloma, and CESS lymphoblastoid cells contain IL-6 RE-BPs that form complexes, with the IL-6-RE, with gel mobilities indistinguishable from those of the corresponding complexes of rat liver cells. The ability to form these complexes was induced by IL-6 in human hepatoma cells with a maximum reached after 4 h and required ongoing protein synthesis. Multiple copies of an 18-bp element containing the IL-6-RE core were sufficient to confer both induction by IL-6 and a synergistic induction by IL-6 plus glucocorticoids to minimal promoters. The synergism was blocked by the receptor antagonist RU486 and thus was dependent on the glucocorticoid receptor (GR). However, the 18-bp element contained no consensus GR-binding site, and recombinant GR did not bind at this sequence. Therefore, the synergism was probably achieved by an indirect effect of a glucocorticoid-activated intermediate gene on the IL-6 RE-BPs. The rat IL-6 RE-BP had a molecular weight of 102 +/- 10 kDa and was thus distinct from NF-IL-6 and IL-6-DBP/LAP. Therefore, IL-6 must activate two different classes of liver acute-phase genes through at least two different nuclear DNA-binding proteins: NF-IL-6/IL-6-DBP/LAP and the IL-6 RE-BP.

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