Significant Reduction In Interleukin-6 Levels Research Articles

Disease Amelioration With Tocilizumab in a Treatment-Resistant Patient With Neuromyelitis Optica

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system in which aberrant antibody responses to the astrocytic water channel aquaporin 4 have been described. Experimental evidence is emerging that NMO is partly driven by the proinflammatory cytokine interleukin 6 (IL-6), which propagates the survival of disease-specific B cell subclasses, and deviates CD4+ T helper cell differentiation toward IL-17-producing T helper 17 cells. Tocilizumab is a recombinant humanized monoclonal antibody against the IL-6 receptor approved for treatment of rheumatoid arthritis. To study clinical and paraclinical effects of tocilizumab in a patient with NMO. Case report. Academic neurology department. A patient with highly active aquaporin 4–seropositive NMO who failed numerous immunosuppressive interventions, including high-dose corticosteroids, mitoxantrone, plasma exchange (PE), rituximab (anti-CD20), and alemtuzumab (anti-CD52), before receiving tocilizumab. Clinical disability, magnetic resonance imaging, cytokines and transcription factors levels in the cerebrospinal fluid, and peripheral blood mononuclear cells. A patient who continued to accumulate neurological disability and magnetic resonance imaging activity while receiving numerous immunoactive therapies stabilized, and eventually improved clinically and on magnetic resonance metrics after treatment initiation with tocilizumab. Treatment and clinical response correlated with a significant reduction of IL-6 levels in the CSF as well as a diminished expression of signal transducer and activator of transcription 3. Tocilizumab might be effective in NMO, here in a patient not responding to leukocyte depletion. Our findings further support data that implicate IL-6 as a critical molecule in the immunopathogenesis of NMO, and a critical role for T cells in the pathogenesis of this disorder.

Impact of Cholecalciferol Treatment on Biomarkers of Inflammation and Myocardial Structure in Hemodialysis Patients Without Hyperparathyroidism

Vitamin D (25-hydroxyvitamin D, 25(OH)D) deficiency, hypovitaminosis D, is highly prevalent in chronic kidney disease patients and is potentially involved with complications in the hemodialysis (HD) population. The aim of this study was to evaluate the impact of cholecalciferol supplementation on biomarkers of mineral metabolism, inflammation, and cardiac function in a group of HD patients presenting with hypovitaminosis D and low intact parathyroid hormone (iPTH) levels. HD patients with iPTH levels of <300 pg/mL, not receiving vitamin D therapy, and presenting with 25(OH)D levels of <30 ng/mL were enrolled in this prospective study. Oral cholecalciferol was prescribed once a week in the first 12 weeks (50,000 IU) and in the last 12 weeks (20,000 IU) of the study. High-sensitivity C-reactive protein, interleukin-6, and serum albumin were used as inflammatory markers. Echocardiograms were performed on a midweek interdialytic day at baseline and after 6 months of cholecalciferol supplementation. In all, 30 patients were included in the final analysis. We observed a significant increase in serum 25(OH)D levels after 3 months (46.2 ± 14.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) and after 6 months (40.4 ± 10.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) of cholecalciferol supplementation. There were no significant changes in alkaline phosphatase, iPTH, phosphorus, and serum albumin levels, but there was a slight but significant increase in calcium levels after 6 months of cholecalciferol supplementation (9.4 ± 0.6 mg/dL vs. 9.0 ± 0.6 mg/dL; P = .02). Additionally, we observed a significant reduction in high-sensitivity C-reactive protein levels after 3 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.32 [0.02 to 3.13] mg/L; P = .02) and after 6 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.50 [0.02 to 5.66] mg/L; P = .04) of cholecalciferol supplementation, as well as a significant reduction in interleukin-6 levels (median: 6.44 pg/mL vs. 3.83 pg/mL; P = .018) after 6 months of supplementation. Left ventricular mass index was significantly reduced at the end of supplementation (159 ± 55 g/m(2) vs. 175 ± 63 g/m(2); P = .03). Cholecalciferol supplementation in HD patients was found to be safe and efficient to correct hypovitaminosis D and established little impact on mineral metabolism markers. Additionally, we observed a reduction in important surrogate markers of cardiovascular risk, namely systemic inflammation and left ventricular hypertrophy, suggesting an anti-inflammatory action and possibly an improvement of cardiac dysfunction.

Serum levels of IL-6 and its soluble receptor (sIL-6R) in Waldenström's macroglobulinemia.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays roles in the immune response, inflammation and hematopoiesis. Serum IL-6 levels have reported to reflect disease severity and high tumor burden in multiple myeloma (MM) patients and to correlate with several other laboratory parameters. Serum-soluble IL-6 receptor (sIL-6R) plays an agonist role in IL-6 signaling, enhancing its biological activity tenfold. PURPOSE-METHODS: We measured IL-6 and sIL-6R levels in 11 patients (7 male, 4 female, mean age 66.9 yr) with Waldenström's macrobulinemia (WM) using a commercially available enzyme-linked immunoassay in order to investigate their biological role and to find any possible relationship with disease severity, tumor burden or response to treatment. Serum IL-6 and sIL-6R concentrations at diagnosis were significantly higher than in healthy controls (Mann Whitney U-test, p < 0.001 and p < 0.01, respectively). Patients who were effectively treated had a significant reduction in IL-6 levels (p = 0.017). With regard to sIL-6R levels, no specific tendency was observed. In some of the responsive patients the levels increased whereas in others they decreased. No correlation was found between IL-6 and sIL-6R levels at diagnosis (p = 0.9, r = 0.036) or after treatment (p = 0.083, r = 0.3). Our results suggest that IL-6 may be a marker reflecting tumor burden, disease severity and response to treatment in WM. With regard to sIL-6R, we believe that it does not seem to be of much value, and its role remains to be clarified. However, future studies are needed to confirm and further extend the present results.