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Regulating against the dysregulation: new treatment options in autoinflammation

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Abstract

In autoinflammatory disorders, dysregulation of the innate immune response leads to an excessive cytokine release. The disease course is often characterized by high morbidity and mortality, treatment is mostly difficult and therapeutic options are limited. In most cases, life-long control of ongoing inflammation is necessary in order to improve clinical symptoms and prevent development of damage. Steroids are helpful in many conditions, but the development of serious side effects often limits their long-term use. Other immunosuppressive, steroid-sparing medications are less effective than in the treatment of autoimmune diseases or do not show any effect. So far, anti-IL1α and/or β-blocking agents as well as an IL-6 receptor-blocking monoclonal antibody and, to a lesser extent, TNF-α blocking agents were applied in autoinflammatory disorders and significantly improved the outcome. Although these progresses were made in the last years, there are still numerous challenges in order to improve drug therapy in autoinflammation. This review summarizes the current state of new drug development and discusses advantages and disadvantages of possible targets.

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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

ASC:

Apoptosis-associated speck-like protein containing a CARD

ATP:

Adenosine triphosphate

BHB:

β-hydroxybutyrate

CANDLE:

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

CAPS:

Cryopyrin-associated periodic syndrome

CDC:

Complement-dependent cytotoxicity

DAMP:

Damage-associated molecular pattern

DMSO:

Dimethylsulfoxide

DRD1:

Dopamine receptor 1

DUB:

Deubiquitinase enzymes

FA:

Fatty acid

FCAS:

Familial cold autoinflammatory syndrome

FMF:

Familial Mediterranean fever

HIDS:

Hyper-IgD and periodic fever syndrome

HFD:

High-fat diet

IP-10:

Interferon gamma inducible protein 10

JAK:

Janus-kinase

LFD:

Low fat diet

LPS:

Lipopolysaccharide

NAC:

N-acetyl cysteine

NRTI:

Nucleoside reverse transcriptase inhibitor

NLRP3:

NLR family, pyrin domain containing 3

PAPA:

Pyogenic arthritis, pyoderma gangrenosum and acne syndrome

PAMP:

Pathogen-associated molecular pattern

PG:

Prostaglandins

ROS:

Reactive oxygen species

sJIA:

Systemic juvenile idiopathic arthritis

SAVI:

STING-associated vasculopathy with onset in infancy

STAT-1:

Signal transducers and activators of transcription

TRAPS:

Tumour necrosis factor receptor-associated periodic fever syndrome

TXN:

Thioredoxin

TXNIP:

Thiodoxin-interacting protein

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Acknowledgments

I thank Dr. K. Minden and Dr. L. Martin for critically reading the manuscript.

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  1. Pediatric Pneumology and Immunology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Tilmann Kallinich

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This article is a contribution to the Special Issue on The Inflammasome and Autoinflammatory Diseases - Guest Editors: Seth L. Masters Tilmann Kallinich and Seza Ozen

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Kallinich, T. Regulating against the dysregulation: new treatment options in autoinflammation. Semin Immunopathol 37, 429–437 (2015). https://doi.org/10.1007/s00281-015-0501-9

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