CYTOKINE REGULATION IN THE COURSE OF MULTIPLE MYELOMA PROGRESSION

Abstract

Cytokines are wide-range modifiers of biological reactions. Cytokine regulation provides proliferation, differentiation, cell function, cell-cell and inter-systemic interaction, direction and nature of immune response to invasion of infectious and non-infectious pathogens. There are several distinct groups of cytokines: pro-inflammatory, anti-inflammatory factors, regulators of cellular and humoral immunity etc. A distinct role of cytokines is not excluded for infectious complications accompanying multiple myeloma (MM). Cytokine regulatory effects on immune defense in the organism as a whole, and a balance between proand anti-inflammatory cytokines in blood of MM patients depend on the stage of multiple myeloma progression and possibility of infectious complications. Therefore, the aim of our study was to evaluate proand anti-inflammatory cytokines and cytokine regulation in patients with MM G-immunochemical option. Our study involved 101 patients with MM (IgG-variant), their age ranging between 40 and 76 years. The diagnosis was verified by clinical and laboratory examinations. The G-variant of MM was verified by immunofixation and electrophoresis. The definite diagnosis and disease staging was confirmed by a combination of diagnostic criteria. Heparinized blood samples were taken from the cubital vein in the morning (8 to 9 hours), in fasting state upon admission, prior to the starting a pathogenetic therapy. Dynamic monitoring of patients was carried out over the period of their staying in hospital. All patients were staged according to Durie and Salmon (1975) (stages II, III). At each stage, we discerned two sub-groups: A, without renal disease, B, with renal impairment. The control group consisted of 125 healthy volunteers matched for age and sex with the main group. IL-2, IL-4, IL-8, TNFα, and IFNγ levels in sera of the patients and healthy individuals were determined by enzyme immunoassay kits (JSC “Vector-Best”,Novosibirsk). In the myeloma patients, we have revealed an imbalance between pro-inflammatory (IL-2, IL-8, TNFα, IFNγ), and antiinflammatory cytokines (IL-4), with a predominance of pro-inflammatory factors. This finding does not exclude their potential pathogenetic role in growth and stimulation of tumor progression, and occurrence of infectious complications at any stage of the disease. The disturbances in cytokine regulation in MM patients may manifest as a deviation of cellular immune response by Th-1 way. As seen from our data, TNFα, IL-2 and IL-4 are the most significant cytokines for MM progression.

Keywords

• pro-inflammatory cytokines
• anti-inflammatory cytokines
• regulation
• multiple myeloma