Clinical significance of interleukin-22 in multiple myeloma.

OBJECTIVE: Interleukin-22 (IL-22) is a cytokine participating in many aspects of inflammation. Multiple myeloma (MM) is a malignant disease of plasma cells with characteristic immune deregulation. We estimated serum levels of IL-22 in MM patients, both in activity and remission, in order to apprehend its possible participation in MM biology. METHODS: We measured serum levels of IL-22 along with beta-2 microglobulin (B2M), paraprotein, and interleukin-1beta (IL-1beta), as well as degree of bone marrow infiltration, in 51 patients with active MM and in 22 of them in remission. RESULTS: We found that IL-22 was higher in active MM patients, compared to both controls and patients in remission, and also in patients in remission compared to controls. Moreover, IL-22 was increasing in parallel with the disease stage and also correlated with B2M, IL1-beta, and degree of infiltration. DISCUSSION: We suggest that the elevated levels of IL-22 in active MM patients, in parallel with disease activity, and in positive correlation with IL-1beta, may represent the inflammatory element of the disease. This increased occurrence of IL-22 may enhance myeloma proliferation and growth, and moreover, may participate in the mechanisms of immune deregulation.

Circulating levels of soluble Fas ligand reflect disease progression in multiple myeloma.

Multiple myeloma (MM) plasma cells are apoptosis resistant. The system of Fas with its ligand (Fas-L) participates actively in the extrinsic apoptotic system. In oncology, its role is controversial, since it has been reported both to suppress and promote tumor growth. The aim of this study was to measure serum levels of soluble Fas-L (sFas-L) in patients with active MM and to correlate them with markers of disease activity. We studied 57 patients with active MM, along with 22 healthy controls. We measured serum levels of sFas-L and interleukin-6 (IL-6) by enzyme-linked immunosorbent assays, as well of beta-2 microglobulin (B2M), C-reactive protein (CRP) and lactate dehydrogenase (LDH). We also measured the degree of bone marrow infiltration. All parameters were increased in patients, compared with controls (p < 0.001 for all cases) and also in parallel with disease stage (p < 0.001 for all cases). Positive correlations were noted between serum levels of sFas-L with IL-6, infiltration (p < 0.001 for both cases) and LDH (p < 0.04), but not with CRP and B2M. We suggest that the system of Fas/Fas-L participates actively in MM progression in a complex manner and that serum levels of sFas-L may reflect disease progression. Further studies are needed to determine its usefulness as a marker of disease activity.

Increased serum levels of MIP-1alpha correlate with bone disease and angiogenic cytokines in patients with multiple myeloma.

Many cytokines possess variable roles in the pathogenesis of multiple myeloma. Macrophage inflammatory protein-1alpha (MIP-1alpha) is an osteoclast-activating factor with a major role in myeloma bone disease. The aim of the study was to examine its participation in the angiogenic process of the disease. We measured, by enzyme-linked immunosorbent assays, its serum levels in 56 newly diagnosed myeloma patients, in several skeletal grades and stages of the disease and in 25 healthy controls. Concurrently, we measured serum levels of the angiogenic cytokines basic-fibroblast growth factor, hepatocyte growth factor and interleukin-18. All the above cytokines were higher in myeloma patients (p < 0.001 for all cases) and were increasing in parallel with disease stage (p < 0.001 for all cases) and skeletal grade (p < 0.04 for MIP-1alpha and p < 0.001 for the other cases). Moreover, positive correlations between MIP-1alpha and all the angiogenic cytokines were noted (p < 0.001 for all cases). MIP-1alpha seems to be a predominant factor responsible for the enhancement of bone resorption and increased angiogenesis. The positive correlation between MIP-1alpha and the angiogenic chemoattractants supports the involvement of these factors in the biology of myeloma cell growth. Moreover, they could be used as possible therapeutic targets as well as markers of disease activity.