Serum interleukin‐6 has no discriminatory role in paraproteinaemia nor a prognostic role in multiple myeloma

Schaar, C. G.; Kaiser, Ulrich; Snijder, Simone; Ong, Francisca; Hermans, J.; Franck, Paul; Kluin-Nelemans, Hanneke C.

doi:10.1046/j.1365-2141.1999.01669.x

Cited by 13 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased serum levels of IL-6 have been documented in active MM patients [32]. However, the data are discordant due to differences in assay sensitivity [38]. By intracellular cytokine staining, a sensitive assay that directly analyses the phenotype of cytokine-producing cells, we clearly demonstrated that IL-6 production by activated T cells paralleled serum IL-6 levels and the clinical stage of MM.…”

Section: Discussionmentioning

confidence: 99%

Deregulated cytokine network and defective Th1 immune response in multiple myeloma

Frassanito

Cusmai

Dammacco

2001

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYIntracellular cytokine production by peripheral blood mononuclear cells (PBMC) was analysed in 51 patients with multiple myeloma (MM), 22 with monoclonal gammopathy of undetermined significance (MGUS) and 20 healthy subjects, as a parameter of immunological dysfunction in MM. An increased proportion of T cells and HLA-DR 1 cells producing IL-6 was observed in MM patients with active disease (at diagnosis and relapsing) compared with patients in remission and with MGUS, whereas no difference of IFN-g 1 , IL-2 1 PBMC between patients and controls was evident. Determination of serum cytokine levels demonstrated that the imbalanced IL-6 production by T cells and the defective antitumour Th1 cell activity were related to elevated levels of IL-6 and IL-12. In vitro studies of PHA-and anti-CD3/anti-CD28 MoAbs stimulation of PBMC demonstrated the ability of lymphocytes from MM patients to differentiate towards the Th1 subset in the presence of rIL-12. By contrast, addition of exogenous rIL-6 impaired IFN-g production by rIL-12-prompted T cells. Inhibition of Th1 polarization of the immune response by IL-6 was direct on T cells and not mediated by dendritic cells (DC). Evaluation of the ability of MM-derived DC to stimulate cell proliferation of allogenic T lymphocytes and produce IL-12 in vitro, in fact, suggested that MM-derived DC were functionally active. Taken as a whole, these results indicate that a deregulated cytokine network occurs in active MM. They also suggest that increased IL-6 production by peripheral T lymphocytes contributes to the immune dysfunction observed in MM, and enables tumour cells to escape immune surveillance by preventing the anti-tumour Th1 immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Deregulated cytokine network and defective Th1 immune response in multiple myeloma

Frassanito

Cusmai

Dammacco

2001

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…8 49 73 and 4 cross-sectional studies 55 56 72 84 had recruited controls and participants free from cancer from hospital inpatients or outpatients who were likely to be less healthy than the general population. Only 10 case-control studies had used community controls, 36 64 89 and 1 cross-sectional study 34 had recruited community-living participants.…”

Section: Design and Selection Of Controlsmentioning

confidence: 99%

A systematic review of the association between circulating concentrations of C reactive protein and cancer

Heikkilä

Ebrahim

Lawlor

2007

Journal of Epidemiology & Community Health

357

267

View full text Add to dashboard Cite

The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case-control or cross-sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene-cancer association studies would be valuable in investigating the role of CRP in cancer.

show abstract

“…From a practical standpoint, the ability of TRAIL/Apo2L to overcome the IL-6-mediated protective effect is important since serum IL-6 levels are often elevated in MM patients [69][70][71].…”

Section: Trail/apo2l and Multiple Myelomamentioning

confidence: 99%

Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias

Mitsiades

Mitsiades²,

Poulaki³

et al. 2001

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) is a member of the TNF superfamily of death ligands that selectively induces apoptosis in tumour cells of diverse origins. In this report, we have reviewed recent studies examining TRAIL/Apo2L-induced apoptosis in multiple myeloma (MM), a B-cell malignancy which, in spite of its initial sensitivity to steroids, cytotoxic and high-dose chemotherapy, remains incurable. Recently, we demonstrated that TRAIL/Apo2L induces apoptosis of steroid- and chemotherapy-sensitive and resistant MM cell lines. Moreover, TRAIL/Apo2L selectively induced apoptosis of patient MM tumour cells while sparing non-malignant bone marrow and peripheral blood mononuclear cells. In addition, TRAIL/Apo2L inhibited the growth of human plasmacytomas xenografted into mice. Importantly, TRAIL/Apo2L-induced apoptosis was unaffected by IL-6, a potent growth and survival factor for MM cells which, as we and others have previously shown, blocks various pro-apoptotic signals including Fas ligand, which like TRAIL/Apo2L is also a member of the TNF family of ligands. In view of the potential clinical application of TRAIL/Apo2L to the treatment of MM, we have attempted to discern intracellular mechanisms of action and resistance for TRAIL/Apo2L in MM, along with strategies to increase sensitivity and overcome resistance of MM cells to TRAIL/Apo2L. These studies demonstrated that doxorubicin, an agent which is commonly used to treat MM patients, upregulated the expression of the DR5 death-signalling TRAIL receptor and synergistically enhanced the pro-apoptotic effect of TRAIL on MM cells. Moreover, NF-kappaB inhibitors such as SN50 (a cell permeable inhibitor of NF-kappaB nuclear translocation) as well as the proteasome inhibitor PS-341, which is currently in Phase II clinical trials, also enhanced the pro-apoptotic activity of TRAIL/Apo2L in MM cells. Lastly, TRAIL/Apo2L-induced apoptosis in MM cells was dependent on caspase-8 activation and inhibited by the caspase regulatory proteins FLIP and cIAP2. These studies provide a framework for the use of TRAIL/Apo2L as a single agent or as part of combination therapy for the treatment of MM.

show abstract

Serum interleukin‐6 has no discriminatory role in paraproteinaemia nor a prognostic role in multiple myeloma

Cited by 13 publications

References 31 publications

Deregulated cytokine network and defective Th1 immune response in multiple myeloma

Deregulated cytokine network and defective Th1 immune response in multiple myeloma

A systematic review of the association between circulating concentrations of C reactive protein and cancer

Concepts in the use of TRAIL/Apo2L: an emerging biotherapy for myeloma and other neoplasias

Contact Info

Product

Resources

About