Targeting IL-33/ST2 signaling: regulation of immune function and analgesia.

Abstract

INTRODUCTION:

IL-33 signals through ST2 receptor and promotes inflammation by activating downstream pathways culminating in the production of pro-inflammatory mediators such as IL-1β, TNF-α, and IL-6 in an NF-κB-dependent manner. In fact, compelling evidence has demonstrated the importance of IL-33/ST2 in both innate and adaptive immune responses in diseases presenting pain as an important clinical symptom. Areas covered: IL-33 is a pleiotropic cytokine with varied immune functions. Dysregulation of this pathway has been described as a key step in varied immune responses. Further, IL-33 contributes to peripheral and spinal cord nociceptor neuron sensitization in innate and adaptive inflammatory immune responses as well as in neuropathic and cancer pain. In this sense, targeting IL-33/ST2 signaling is a promising therapeutic approach. Expert opinion: The modulation of IL-33/ST2 signaling represents a possible approach in regulating immune functions. In addition to immune function, strategies targeting IL-33/ST2 signaling pathway display a favorable preclinical analgesic profile in both acute and chronic models of pain. Therefore, IL-33-targeting therapies represent a potential target for the development of novel analgesic drugs given that IL-33 activates, for instance, neutrophils, mast cells, macrophages, astrocytes, and microglia that are important cells in the induction and maintenance of chronic pain states.

• Authors: Victor Fattori, Miriam S N Hohmann, Ana C Rossaneis, Marilia F Manchope, Jose C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Waldiceu A Verri Jr
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 21 Issue 12 Pg. 1141-1152 (12 2017) ISSN: 1744-7631 [Electronic] England
• PMID: 29076792 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Cytokines
• IL1RL1 protein, human
• IL33 protein, human
• Inflammation Mediators
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-33

Topics

• Acute Pain (drug therapy, immunology)
• Analgesics (pharmacology)
• Animals
• Chronic Pain (drug therapy, immunology)
• Cytokines (immunology)
• Drug Design
• Humans
• Inflammation (drug therapy, immunology)
• Inflammation Mediators (metabolism)
• Interleukin-1 Receptor-Like 1 Protein (metabolism)
• Interleukin-33 (immunology, metabolism)
• Molecular Targeted Therapy
• Signal Transduction (drug effects)