PMID- 38077370
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240329
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - The role of the interleukin-36 axis in generalized pustular psoriasis: a review 
      of the mechanism of action of spesolimab.
PG  - 1292941
LID - 10.3389/fimmu.2023.1292941 [doi]
LID - 1292941
AB  - Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin 
      disorder characterized by recurrent flares associated with skin erythema, 
      desquamation, and widespread superficial sterile pustules, which may be severe 
      ("lakes of pus"). Systemic symptoms are often present, including malaise, fever, 
      and skin pain. In GPP, innate immune responses are driven by abnormal activation 
      of the interleukin (IL)-36-chemokine-neutrophil axis and excessive neutrophil 
      infiltration. This review highlights the IL-36 pathway in the context of the IL-1 
      superfamily and describes how unopposed IL-36 signaling can lead to the 
      development of GPP. Targeted inhibition of the IL-36 receptor (IL-36R) is an 
      attractive therapeutic strategy in the treatment of GPP, including flare 
      prevention and sustained disease control. Spesolimab is a first-in-class, 
      humanized, monoclonal antibody that binds specifically to the IL-36R and 
      antagonizes IL-36 signaling. Spesolimab was approved by the US Food and Drug 
      Administration in September 2022 to treat GPP flares in adults and was 
      subsequently approved for GPP flare treatment in other countries across the 
      world. Anti-IL-36R therapy, such as spesolimab, can mitigate flares and address 
      flare prevention in GPP, presumably through rebalancing IL-36 signaling and 
      modulating the pro-inflammatory response of the downstream effectors.
CI  - Copyright (c) 2023 Hawkes, Visvanathan and Krueger.
FAU - Hawkes, Jason E
AU  - Hawkes JE
AD  - Integrative Skin Science and Research and Pacific Skin Institute, Sacramento, CA, 
      United States.
FAU - Visvanathan, Sudha
AU  - Visvanathan S
AD  - Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim 
      Pharmaceuticals, Inc., Ridgefield, CT, United States.
FAU - Krueger, James G
AU  - Krueger JG
AD  - Laboratory for Investigative Dermatology, The Rockefeller University, New York, 
      NY, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20231121
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 5IB2J79MCX (spesolimab)
RN  - 0 (Interleukins)
SB  - IM
MH  - United States
MH  - Adult
MH  - Humans
MH  - *Psoriasis
MH  - Interleukins/metabolism
MH  - Skin
MH  - *Skin Diseases, Vesiculobullous
PMC - PMC10703363
OTO - NOTNLM
OT  - GPP
OT  - IL-1
OT  - IL-36
OT  - IL36RN
OT  - generalized pustular psoriasis
OT  - psoriasis
OT  - spesolimab
COIS- JH serves on the medical board and scientific advisory committee of the National 
      Psoriasis Foundation, is a councilor for the International Psoriasis Council, and 
      has been a paid consultant for AbbVie, Arcutis, BMS, Boehringer Ingelheim, Eli 
      Lilly and Company, Janssen, LEO, Novartis, Pfizer, Regeneron-Sanofi, Sun 
      Pharmaceutical, UCB, VisualDx, and UpToDate. SV is an employee of Boehringer 
      Ingelheim Pharmaceuticals, Inc. JK has received grants from and been an 
      investigator for Boehringer Ingelheim; received personal fees from AbbVie, 
      Baxter, Biogen Idec, Delenex Therapeutics, Kineta, Sanofi, Serono, and XenoPort; 
      and received grants from Amgen, Bristol Myers Squibb, Dermira, Innovaderm 
      Research, Janssen, Kadmon, Kyowa Kirin, Eli Lilly, Merck, Novartis, Parexel, and 
      Pfizer.
EDAT- 2023/12/11 12:43
MHDA- 2023/12/17 09:44
PMCR- 2023/01/01
CRDT- 2023/12/11 06:29
PHST- 2023/09/12 00:00 [received]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/12/17 09:44 [medline]
PHST- 2023/12/11 12:43 [pubmed]
PHST- 2023/12/11 06:29 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1292941 [doi]
PST - epublish
SO  - Front Immunol. 2023 Nov 21;14:1292941. doi: 10.3389/fimmu.2023.1292941. 
      eCollection 2023.