Soluble interleukin‐6 receptor as a prognostic factor in multiple myeloma

Abstract

Interleukin-6 (IL-6) is a major growth factor for the clonal malignant plasma cells in multiple myeloma (MM). The effect of IL-6 may be enhanced by soluble IL-6 receptor (sIL-6R). As there is a clinical need for improved stratification of MM patients at diagnosis, we have studied the role of sIL-6R as a prognostic marker in 207 newly diagnosed MM patients. Serum sIL-6R concentration was above the upper reference limit in 47% of the patients at diagnosis. The concentrations of sIL-6R and two other prognostic factors, IL-6 and beta-2 microglobulin (beta 2M), were all significantly higher in the patients who died within 3 years compared with those who survived. However, serum sIL-6R did not show linear correlation with IL-6 or beta 2M levels. In univariate logistic regression analysis sIL-6R was a significant predictor of 3-year mortality. Kaplan-Meier analysis showed that raised levels of sIL-6r were associated with shorter survival. When the patients were stratified into four groups according to their serum IL-6 and sIL-6R levels the patients with normal serum levels of both parameters had clear survival benefit. As beta 2M was the most powerful prognostic factor in the multivariate analysis, the patients were also stratified according to their serum beta 2M and sIL-6R levels. The patients with raised levels of both beta 2M and sIL-6R had shorter survival than the patients in the other three groups. Thus, measurement of these parameters at diagnosis would help to stratify MM patients.

Inverse correlation of interleukin-6 with soluble interleukin-6 receptor after transplantation of bone marrow or peripheral blood stem cells

“…(2) A second was reported that patients with raised levels of both sILpossible mechanism for the decrease of the serum sIL-6R 6R and ␤2-microglobulin had shorter survival than other level is a consumption of circulating sIL-6R due to formapatient groups indicating its prognostic value for the tion of IL-6/sIL-6R complexes in the presence of IL-6 and stratification of patients. 36 subsequent binding and internalization of the complexes by In the present work, we show an increase of serum ILtarget cells expressing the gp130 signal transducing protein. 6 during the aplastic phase after bone marrow or peripheral Circulating IL-6/sIL-6R complexes are found in patient blood stem cell transplantation culminating at day 6 folsera, 13,31 and it has been reported that IL-6 can down-regulowed by a decrease to baseline values.…”

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

“…For myeloma it is well known that interleukin-6 (IL-6) plays a crucial role in the cytokine network, regulating the growth and survival of myeloma cells and stimulating the acute-phase protein synthesis, notably C-reactive protein (CRP) (Lauta, 2003). Several authors investigating serum IL-6 in relation to acute-phase reactants and survival in myeloma patients report not only significantly shorter survival for those with higher concentrations of IL-6 compared with patients who had normal concentrations (Ludwig et al, 1991;Pulkki et al, 1996;Papadaki et al, 1997;Stasi et al, 1998), but also demonstrate a strong positive correlation between IL-6 and CRP (Tienhaara et al, 1994;Pelliniemi et al, 1995;Kyriakou et al, 1997;Biro et al, 1998;Alexandrakis et al, 2003). As an assessment of infection status at the time of surgery was made, CRP rather appears to act as a surrogate marker for IL-6 activity and proliferative status of bone marrow plasma cells and has been regarded as a powerful prognostic marker in patients with multiple myeloma, than a sign for preoperative infectious states.…”

Vascular endothelial growth factor and its receptors in multiple myeloma

“…Elevated serum IL-6 receptor concentrations are associated with a poor prognosis in MM and used as an indicator of disease activity. 59 Other cytokines, including TNFa, have been reported to be involved in the control of VEGF production by myeloma cells. 60 Moreover, VEGF directly, or indirectly through its stimulatory activity on TNF-a and Il-b1 stimulates the activation of osteoclasts and thus contributes to the lytic lesions in MM.…”