The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab
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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1292941/full |
| _version_ | 1797488628871462912 |
|---|---|
| author | Jason E. Hawkes Sudha Visvanathan James G. Krueger |
| author_facet | Jason E. Hawkes Sudha Visvanathan James G. Krueger |
| author_sort | Jason E. Hawkes |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:05:58Z |
| format | Article |
| id | doaj.art-1ebaf70efb874a9e8f9a85113d0f2d54 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-10T00:05:58Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1ebaf70efb874a9e8f9a85113d0f2d542023-11-23T16:08:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12929411292941The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimabJason E. Hawkes0Sudha Visvanathan1James G. Krueger2Integrative Skin Science and Research and Pacific Skin Institute, Sacramento, CA, United StatesTranslational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United StatesLaboratory for Investigative Dermatology, The Rockefeller University, New York, NY, United StatesGeneralized 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1292941/fullgeneralized pustular psoriasisGPPpsoriasisIL-36IL-1IL36RN |
| spellingShingle | Jason E. Hawkes Sudha Visvanathan James G. Krueger The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab Frontiers in Immunology generalized pustular psoriasis GPP psoriasis IL-36 IL-1 IL36RN |
| title | The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab |
| title_full | The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab |
| title_fullStr | The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab |
| title_full_unstemmed | The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab |
| title_short | The role of the interleukin-36 axis in generalized pustular psoriasis: a review of the mechanism of action of spesolimab |
| title_sort | role of the interleukin 36 axis in generalized pustular psoriasis a review of the mechanism of action of spesolimab |
| topic | generalized pustular psoriasis GPP psoriasis IL-36 IL-1 IL36RN |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1292941/full |
| work_keys_str_mv | AT jasonehawkes theroleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab AT sudhavisvanathan theroleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab AT jamesgkrueger theroleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab AT jasonehawkes roleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab AT sudhavisvanathan roleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab AT jamesgkrueger roleoftheinterleukin36axisingeneralizedpustularpsoriasisareviewofthemechanismofactionofspesolimab |