Successful Treatment of a Mesangial Proliferative Glomerulonephritis with Interstitial Nephritis Associated with Castleman's Disease by an Anti-interleukin-6 Receptor Antibody (Tocilizumab)

Otani, Naoko; Morishita, Yoshiyuki; Oh, Iekuni; Saito, Osamu; Muto, Shigeaki; Kusano, Eiji

doi:10.2169/internalmedicine.51.6555

Cited by 14 publications

(4 citation statements)

References 14 publications

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“…Normal levels of IL-6 expression are conducive to immunological homeostasis, whereas excessive production can cause a series of inflammatory lesions, leading to such diseases as rheumatoid arthritis, Crohn’s disease, and glomerulonephritis. 26 – 28 Transgenic mice overexpressing IL-6 developed a variety of disorders, including pulmonary fibrosis, hypertension, multiple myeloma, plasmacytosis, and neurological disease. 29 – 31 …”

Section: Introducing Il-6mentioning

confidence: 99%

IL-6 Plays a Crucial Role in HBV Infection

Lan

Chang

et al. 2015

JCTH

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Interleukin-6 (IL-6), a cytokine mainly produced by activated monocytes, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-6 in regulating immunity to infections are currently being defined. Remarkably, IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control. However, as a mediator of inflammation, IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-6 as an immunoregulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future, as they should foster the strengths of IL-6 while circumventing potential drawbacks.

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Section: Introducing Il-6mentioning

confidence: 99%

IL-6 Plays a Crucial Role in HBV Infection

Lan

Chang

et al. 2015

JCTH

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“…Therefore, we sought to identify the cytokines and/or chemokines responsible for the development of RPGN in SCG/Kj mice by using a microsphere‐based multiplex protein assay, and to investigate their clinical potential as a target of monoclonal antibody therapy. A monoclonal antibody against IL‐6R, tocilizumab, has been used to treat inflammatory diseases such as Castleman disease , systemic juvenile idiopathic arthritis , and RA . Because the IL‐6 signaling pathway plays an important role in autoantibody production, it should be studied in relation to MPO–ANCA production in SCG/Kj mice.…”

mentioning

confidence: 99%

Correlation of interleukin‐6 and monocyte chemotactic protein‐1 concentrations with crescent formation and myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti‐interleukin‐6 receptor antibody or mizoribine

Nagao

Kusunoki

Iwamura

et al. 2013

Microbiology and Immunology

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Myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN. The serum concentration of soluble IL-6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio-Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3 þ B220 þ T cell subset in the spleen determined by a flow cytometry. Concentrations of IL-6 and monocyte chemotactic protein-1 were significantly correlated with the percentages of crescent formation. Anti-IL-6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL-6 in the development of RPGN. MPO-ANCA titers decreased after administration of anti-IL-6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL-6-mediated signaling is involved in the production of MPO-ANCA.

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“…Second, TCZ treatments cannot always eliminate renal amyloid deposits in patients with AA amyloidosis. Recent case reports have revealed that TCZ treatments decrease proteinuria and improve or preserve renal function in patients with renal AA amyloidosis [8, 12–14]; however, the present patient's renal involvement was refractory to TCZ treatment.…”

Section: Discussionmentioning

confidence: 59%

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

Matsui

Okayama

Tsushima

et al. 2014

Case Reports in Nephrology

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Systemic reactive AA amyloidosis is a life-threatening complication of chronic inflammatory diseases. Anti-interleukin-6 receptor, tocilizumab (TCZ), has been shown to improve clinical symptoms of patients with AA amyloidosis, accompanied with regression of the amyloid deposition. We report a case of AA amyloidosis evaluated by histology of multiple organs before and after TCZ treatment. A woman in her 60s with rheumatoid arthritis was referred to our hospital because of cardiac and renal dysfunction. A gastric and renal biopsy revealed the deposition of AA amyloid, and echocardiography revealed concentric left ventricular hypertrophy. Her estimated glomerular filtration rate was decreased to 8.6 mL/min/1.73 m2, and B-type natriuretic peptide, C-reactive protein, and serum amyloid A protein were significantly elevated. TCZ treatments markedly decreased her serum amyloid A protein and C-reactive protein levels, but hemodialysis was required 1 year later. Endoscopic gastric rebiopsy 3 years after initiation of TCZ treatments revealed the regression of amyloid deposition and echocardiography revealed improvement of her left ventricular hypertrophy. However, a renal rebiopsy revealed that the amyloid deposition had not regressed. In conclusion, these observations suggest that the therapeutic effects of TCZ can vary among organs in patients with AA amyloidosis.

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Successful Treatment of a Mesangial Proliferative Glomerulonephritis with Interstitial Nephritis Associated with Castleman's Disease by an Anti-interleukin-6 Receptor Antibody (Tocilizumab)

Cited by 14 publications

References 14 publications

IL-6 Plays a Crucial Role in HBV Infection

IL-6 Plays a Crucial Role in HBV Infection

Correlation of interleukin‐6 and monocyte chemotactic protein‐1 concentrations with crescent formation and myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti‐interleukin‐6 receptor antibody or mizoribine

Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis

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