IL-6 levels among the MCD patients tested in this study were correlated with levels of albumin, hemoglobin, triglyceride, total cholesterol, C-reactive protein, fibrinogen and immunoglobulin G (Spearman's correlation coefficient, ;r; = 0.28-0.59).
Interleukin-6 (IL-6) is a pleiotropic cytokine which is involved in a large range of physiological processes in our body such as pro-inflammatory, anti-inflammation, differentiation of T-cells and is reported to be a key pathological factor in MCD.
Viral IL-6 is also considered to contribute significantly to HHV-8-associated pathogenesis, since vIL-6 can promote cell proliferation, cell survival, and angiogenesis that are characteristic of HHV-8-associated Kaposi's sarcoma, PEL and multicentric Castleman's disease (MCD), in addition to proinflammatory activities observed in MCD-like "Kaposi's sarcoma-associated herpesvirus-induced cytokine syndrome."
The high titer of serum vascular endothelial growth factor and interleukin-6 could explain common characteristic vascular lesions in both TAFRO syndrome and POEMS syndrome/MCD.
Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown.
The results of several studies have shown that most MCD symptoms and abnormal laboratory results are improved by anti-IL-6MCD treatments, such as tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, an anti-IL-6 antibody.
However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD.
On the basis of the favourable results obtained in the subset of multicentric Castleman disease (MCD), Siltuximab, a chimeric, human-murine, immunoglobulin (Ig) Gk monoclonal antibody directed against human IL-6 has been evaluated in haematological malignancies such as multiple myeloma, myelodisplastic syndromes and non Hodgkin lymphomas.
The data were obtained from two phase 2, double-blind, placebo-controlled trials designed to test the efficacy of sirukumab in RA (N=176) or of siltuximab in MCD (N=65), and were analyzed post hoc to investigate the effects of these IL-6 antibodies on depressive symptoms.
KSHV encodes a viral homolog of human IL-6, accounting for its role in MCD, while recent evidence shows an association between IL-6 receptor polymorphisms and idiopathic MCD.
These LANA+ B cells proliferated and exhibited similarities to the cells characteristic of MCD (IgMl-expressing plasmablasts), including blasting morphology with elevated expression of Ki67, variable expression of CD27, and high levels of IgM and IL-6 receptor.
Recent advances in dissecting the pathogenesis of these diseases have indicated that the viral cytokine IL-6 and the cellular cytokines/growth factors IL-10, IL-6, stromal cell-derived factor 1, and vascular endothelial growth factor are important contributors to the growth, survival, and spread of PEL and MCD and are therefore potential targets for drug development.
Clinically, pegylated-liposomal doxorubicin induced regression of not only KS, but also lymphadenopathy of the MCD lesion with a decrease in KSHV load and human interleukin-6 in the blood.
Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation.