Tocilizumab is effective for pulmonary hypertension associated with multicentric Castleman’s disease

Abstract

A 38-year-old man, diagnosed as having multicentric Castleman's disease (plasma cell type) in 1995, had been treated with melphalan and prednisolone or prednisolone alone, but there was no remarkable response. In 2002, he was admitted to our hospital with a chief complaint of increasing dyspnea on effort. Laboratory data showed high serum IgG (10050 mg/dl), interleukin-6 (37.9 ng/ml), and vascular endothelial growth factor (VEGF 1920 pg/ml) levels. In addition, serum viscosity was very high (6.0 cp). Electrocardiogram, echocardiogram, and cardiac catheterization demonstrated pulmonary hypertension (PH). There were no other demonstrable causes of PH suggesting that PH was due to hyperviscosity syndrome and high VEGF level. He was treated with plasmapheresis, resulting in a transient improvement of dyspnea. Then, he was given humanized anti-interleukin-6 receptor antibody (tocilizumab), which resulted in the dramatic improvement of dyspnea and PH a few weeks later. PH is a rare complication of MCD, and could be successfully treated with tocilizumab.

Plasma Cytokines and Portopulmonary Hypertension in Patients With Cirrhosis Waiting for Orthotopic Liver Transplantation

“…[26][27][28] Although there is only 1 case report in the literature, we believe that the role of anti-IL-6 receptor tocilizumab should be evaluated in selected patients affected by PPHTN. 29 …”

KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation

“…Murine models can recapitulate the clinical manifestations of MCD even in the absence of KSHV simply by dysregulating IL-6 (6,7). Similarly, IL-6 receptor (IL-6R) blocking therapy can ameliorate MCD symptoms in some patients (8)(9)(10). While the majority of KSHV-infected B cells in MCD express IL-6R (3), the precise effects of IL-6 on KSHVinfected B cells remain unknown.…”

World Health Organization Group I Pulmonary Hypertension

“…Animal data supported a role of IL-6 in promoting PAH as IL-6 knockout mice were resistant to hypoxia-induced PH [44], while overexpression of IL-6 induced PH [45]. Moreover, use of the IL-6 receptor antibody Tocilizumab reduced the severity of PH in patients with Castelman’s disease [46, 47], providing further evidence that elevated IL-6 levels promote a more severe PAH phenotype.…”