ANTI-INTERLEUKIN 6 (IL-6) RECEPTOR ANTIBODY SUPPRESSES CASTLEMAN'S DISEASE LIKE SYMPTOMS EMERGED IN IL-6 TRANSGENIC MICE

Cytokine ◽  
2002 ◽  
Vol 20 (6) ◽  
pp. 304-311 ◽  
Author(s):  
Asao Katsume ◽  
Hiroyuki Saito ◽  
Yoshiki Yamada ◽  
Keigo Yorozu ◽  
Otoya Ueda ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Castleman's Disease ◽  
Receptor Antibody

Monitoring of Serum Hepcidin-25 in Multicentric Castleman’s Disease Patients Treated with Tocilizumab, an Anti-Interleukin-6 Receptor Antibody.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3686-3686
Author(s):  
Hiroshi Kawabata ◽  
Naohisa Tomosugi ◽  
Junya Kanda ◽  
Chisaki Mizumoto ◽  
Yasuhiro Tanaka ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Microcytic Anemia ◽  
Castleman's Disease ◽  
Multicentric Castleman’S Disease ◽  
Hepcidin Level ◽  
Receptor Antibody ◽  
Serum Hepcidin ◽  
Multicentric Castleman's Disease

Abstract Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder with systemic manifestations such as lymphadenopathy, fever and microcytic anemia. Over-production of interleukin-6 (IL-6) has been speculated to be a key event in the pathogenesis of this disorder. IL-6 is known to stimulate hepatic expression of hepcidin, a central regulator of body iron homeostasis. We developed a SELDI-TOF mass spectrometry-based semi-quantitative method for serum hepcidin-25 (Tomosugi N, et al. Blood108, 1381–7, 2006). Utilizing this method, we previously reported a rapid decrease in serum hepcidin-25 in two MCD patients after administration of tocilizumab, an anti-IL-6 receptor antibody (Kawabata H, et al. Haematologica92, 857–8, 2007). Recently, by introducing liquid chromatography tandem mass-spectrometry and an isotopic hepcidin as an internal standard, we developed another serum hepcidin quantification system with very small intra- and inter-assay CVs. Utilizing this new method in this study, we further evaluated the clinical relevance of monitoring serum hepcidin in MCD patients treated with tocilizumab. Serum hepcidin-25 was monitored in 5 MCD cases including two previously reported cases (Cases 1 and 2). Tocilizumab (8 mg/kg body weight) was administered intravenously at 2-week intervals. This study was approved by the Ethics Committee of Kyoto University Graduate School and the Faculty of Medicine. Written informed consent was obtained from each patient. The initial levels of serum hepcidin-25 before tocilizumab treatment varied widely, between 14 and 256 ng/ml (normal range, 22 ± 12 ng/ml). In all cases, rapid reduction of serum hepcidin-25 was observed after the initial dose of tocilizumab, followed by decreases of C-reactive protein and gradual improvement of anemia (Table 1). In Case 5, the initial hepcidin level was extremely high (256 ng/ml) and it decreased only slightly after tocilizumab administration. In this case, the serum hepcidin level on day 35 remained considerably elevated (90.5 ng/ml) even after 3 doses of tocilizumab. On the same day, an anti-tocilizumab antibody was detected in the serum, and this medication was discontinued. In the other 4 cases, serum hepcidin levels decreased below the upper normal limit within 2 weeks. After 16 weeks treatment with tocilizumab, Hb increased from 5.7 to 11.2 g/dl in Case 1, from 10.2 to 11.9 g/dl in Case 2, from 6.3 to 11.0 g/dl in Case 3 and from 8.2 to 13.7 g/dl in Case 4. There were no apparent side effects in these 4 cases. These findings imply that inadequate levels of serum hepcidin caused by overproduction of IL-6 are associated with the pathogenesis of microcytic anemia observed in MCD patients. Monitoring of serum hepcidin may be useful to evaluate the efficacy of tocilizumab in MCD cases. Table 1 Case 1 Case 2 Case 3 Case 4 Case 5 Pre/Day14 Pre/Day14 Pre/Day14 Pre/Day14 Pre/Day14 Hepcidin-25 (ng/ml) 44.8/2.2 55.5/24.6 14/0.8 43.5/1.5 256/166 CRP (mg/dl) 24.3/5.4 11.7/4.1 16.9/3.6 7.6/0.2 11.9/6.8 Hb (g/dl) 5.7/9.2 10.2/11.2 6.3/7.9 8.2/9.4 6.5/7.4

scholarly journals Effectiveness of Humanized Anti-interleukin-6 Receptor Antibody (tocilizumab) for Castleman's Disease Mainly with Pulmonary Involvement

2007 ◽  
Vol 96 (5) ◽  
pp. 988-990 ◽  
Author(s):  
Nobuhito Ohno ◽  
Sayuri Fujiyama ◽  
Masaomi Ooi ◽  
Kouichi Haraguchi ◽  
Masahito Tokunaga ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Pulmonary Involvement ◽  
Castleman's Disease ◽  
Receptor Antibody ◽  
Interleukin 6 Receptor

Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Norihiro Nishimoto ◽  
Mitsuko Sasai ◽  
Yoshihito Shima ◽  
Masashi Nakagawa ◽  
Tomoshige Matsumoto ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Plasma Cell ◽  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Serum Levels ◽  
Secondary Amyloidosis ◽  
Castleman's Disease ◽  
Follicular Hyperplasia ◽  
Receptor Antibody ◽  
Systemic Manifestations

Abstract Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)

Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Norihiro Nishimoto ◽  
Mitsuko Sasai ◽  
Yoshihito Shima ◽  
Masashi Nakagawa ◽  
Tomoshige Matsumoto ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Plasma Cell ◽  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Serum Levels ◽  
Secondary Amyloidosis ◽  
Castleman's Disease ◽  
Follicular Hyperplasia ◽  
Receptor Antibody ◽  
Systemic Manifestations

Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)

scholarly journals Anti-interleukin-6 Receptor Antibody (Tocilizumab) Treatment of Multicentric Castleman's Disease

2007 ◽  
Vol 46 (11) ◽  
pp. 771-774 ◽  
Author(s):  
Masashi Matsuyama ◽  
Takeshi Suzuki ◽  
Hiroto Tsuboi ◽  
Satoshi Ito ◽  
Mizuko Mamura ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Castleman’S Disease ◽  
Castleman's Disease ◽  
Multicentric Castleman’S Disease ◽  
Receptor Antibody ◽  
Interleukin 6 Receptor ◽  
Multicentric Castleman's Disease
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