Successful treatment of recurrent pleural and pericardial effusions with tocilizumab in a patient with systemic lupus erythematous

Ocampo, Vanessa; Haaland, Derek; Legault, Kimberly; Mittoo, Shika; Aitken, Emily

doi:10.1136/bcr-2016-215423

Cited by 20 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another phase II study in SLE patients with the humanized monoclonal antibody tocilizumab against the chain of the IL-6 receptor, showed a reduction of auto-antibodies production and plasma-cells and significant clinical improvement especially in case of arthritis and fatigue (Illei et al, 2010). Finally a case report demonstrated the efficacy of tocilizumab in lupus serositis (Kamata and Minota, 2012; Ocampo et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

et al. 2019

View full text Add to dashboard Cite

Introduction: P2X7R is an extracellular ATP-gated receptor involved in inflammatory and autoimmune processes mainly acting through NLPR3-inflammasome activation and IL-1β release, also implicated in lymphocyte proliferation and cellular apoptosis. Several observations from animal models and patients’ studies highlight a possible link between P2X7R-NLRP3 axis and Systemic Lupus Erythematosus (SLE) pathogenesis. The P2X7R-inflammasome axis in addition to the direct production of IL-1β and IL-18, indirectly mediates the release of other cytokines implicated in the pathogenesis of SLE, such as IL-6. The aim of this study was to investigate the role of P2X7R and NLRP3-inflammasome in SLE. Methods: Forty-eight SLE patients, 16 with (SLE-S) and 32 without (SLE-NS) history of serositis, and 20 healthy control (HC) subjects were enrolled. Demographic, clinical, and therapeutic data were collected. IL-1β and IL-6 plasma levels were evaluated by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by Ficoll gradient sedimentation and employed as follows: (1) evaluation of P2X7R and NLRP3 expression by RT-PCR; (2) determination of P2X7R activity as Benzoyl ATP (BzATP)-induced [Ca 2+ ] i increments using Fura-2-AM fluorescent probe; (3) isolation of monocytes/macrophages and assessment of in vitro IL-1β and IL-6 release following stimulation with lipopolysaccharide (LPS) and BzATP, either separately or in combination. Results: Plasma IL-1β levels were unmodified in SLE respect to HC whereas IL-6 levels were higher in SLE than in HC, resulting significantly increased in SLE-S. Macrophages isolated from SLE patients released lower quantities of IL-1β after stimulation with BzATP, whereas IL-6 release was significantly augmented in SLE-NS respect to both HC and SLE-S after all types of stimulation. The [Ca 2+ ]i increase following BzATP stimulation was significantly lower in PBMCs from SLE patients than in PBMCs from HC. RT-PCR showed significantly reduced P2X7R and significantly augmented NLRP3 expression in PBMCs from SLE patients. Conclusion: Our data indicate reduced P2X7R expression and function in SLE patients compared with HC and, conversely, increased IL-6 signaling. The possible consequences of reduced P2X7R, mainly on cytokines network deregulation and lymphocyte proliferation, will be further investigated as well as the role of IL-6 as a possible therapeutic target especially in lupus serositis.

show abstract

Section: Discussionmentioning

confidence: 99%

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The tocilizumab is another monoantibody directed against IL-6 receptor and blocks the downstream signal pathway by which it modulates the function of IL-6R expressing T and B cells. This agent was successfully administrated to patients with lupus-associated serositis [ 53 ], massive pericarditis, and glomerulonephritis [ 52 , 54 ]. In autoimmunity, combination therapy with anti-IL-1 β and anti-IL-6 antibody has not been tested so far.…”

Section: Discussionmentioning

confidence: 99%

IL-1βand IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype

Cai

Zhang

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1β, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1β) were measured in sera of familial SLE patients (n = 3), noninherited SLE patients (n = 108), and healthy controls (n = 80). Results. Three familial SLE patients and 5 noninherited SLE cases are with features of RF+IgE+. These RF+IgE+ SLE patients expressed significantly higher levels of IL-1β and IL-6 than the other SLE patients (P < 0.05). IL-6 correlated with both IgE and IL-1β levels in RF+IgE+ SLE patients (r2 = 0.583, P = 0.027; r2 = 0.847, P = 0.001), and IgE also correlated with IL-1β (r2 = 0.567, P = 0.031). Conclusion. Both IL-1β and IL-6 are highly expressed cytokines in RF+IgE+ SLE subtype which may be related to the pathogenesis of this special SLE subtype and provide accurate treatment strategy by neutralizing IL-1β and IL-6.

show abstract

“…An analysis of circulating T and B cell subsets in patients with SLE showed that TCZ decreased the frequency of plasmablasts/plasma cells and memory B cells but increased the concentrations of antigen-inexperienced B cells and naïve T cells, suggesting the restoration of B and T cell homeostasis [ 157 ]. A case report also indicated that TCZ was effective for recurrent pleural and pericardial effusion in patients with SLE [ 158 ]. Further clinical studies are required to confirm the efficacy of TCZ on SLE.…”

Section: Therapeutic Targeting Of Il-6 In Diseasesmentioning

confidence: 99%

The Two-Faced Cytokine IL-6 in Host Defense and Diseases

Narazaki

Kishimoto

2018

IJMS

162

129

View full text Add to dashboard Cite

Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.

show abstract

Successful treatment of recurrent pleural and pericardial effusions with tocilizumab in a patient with systemic lupus erythematous

Cited by 20 publications

References 31 publications

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

P2X7 Receptor Expression in Patients With Serositis Related to Systemic Lupus Erythematosus

IL-1βand IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype

The Two-Faced Cytokine IL-6 in Host Defense and Diseases

Contact Info

Product

Resources

About