Secret messengers: Extracellular RNA communication in the immune system*

2021 ◽  
Author(s):  
Grant K Nation ◽  
Cherie E Saffold ◽  
Heather H Pua
Keyword(s):  
Immune System ◽  
Extracellular Rna

Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study

Lupus ◽  
2016 ◽  
Vol 26 (8) ◽  
pp. 825-834 ◽  
Author(s):  
D J Burge ◽  
J Eisenman ◽  
K Byrnes-Blake ◽  
P Smolak ◽  
K Lau ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Fusion Protein ◽  
Lupus Erythematosus ◽  
Controlled Study ◽  
Systemic Lupus ◽  
Double Blind ◽  
Extracellular Rna ◽  
Immune System Activation ◽  
Fc Fusion Protein

Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.

Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Associative Learning ◽  
Placebo Response ◽  
Immunosuppressive Drug ◽  
Immune Functions ◽  
Placebo Effects ◽  
New Therapeutic Approaches ◽  
Biological Variables ◽  
Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

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