Correlation of IL-31 serum levels with severity of atopic dermatitis
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IL-31 is a pruritogenic cytokine produced by TH2 cells infiltrating atopic dermatitis skin, and its levels correlate with disease severity.
“IL-31 is a prominent pruritogenic cytokine produced by infiltrating TH2 cells in AD and correlates with disease severity97,184,185.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [185]
In “Correlation of IL-31 serum levels with severity of atopic dermatitis” (page not provided), the authors report that serum IL-31 correlates with AD severity and describe evidence for a role in pruritus. They identify skin-infiltrating T cells as possible sources and report that IL31 mRNA correlates with TH2 cytokines, but do not establish that infiltrating TH2 cells produce IL-31 in AD skin. (LLM, conf=0.85)
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“On the other hand, AD has been found to be associated with variants of a number of genes primarily involved in immune pathways, including IL-4R, IL-18, IL-31, etc. [14–16] The complex immune dysregulation in AD is increasingly being recognized.”
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“In humans, IL-31 serum levels are higher in AD eompared with non-atopie healthy eontrols, and eorrelate with disease aetivity (14).”
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“Several investigators interested in the role of IL-31 in human AD have already extended their evaluations to the protein level and have generated data correlating serum levels of IL-31 to disease severity.(3,7) Specifically, studies have shown IL-31 to be elevated in the serum of human AD patients compared with health…”
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“IL-31 is also increased in the serum of AD patients [43,67], and increased blood levels of this itch-promoting cytokine positively correlate with disease severity [43,44].”
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“In terms of the systemic expression of IL-31, serum levels were higher in AD patients than in the non-atopic healthy individuals and correlated with disease activity [12].”
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“compared to healthy individuals [7], and correlated positively with disease severity [8].”
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“In addition, IL-31 can also be found in the circulatory system, as patients with atopic dermatitis have IL-31 serum levels correlating with disease severity and Th2 cytokines (Raap et al., 2008).”
BackgroundSelf-citationInterleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis
Kuzumi, A., Yoshizaki, A., Matsuda, K. M., Kotani, H., Norimatsu, Y., Fukayama, M., Ebata, S., Fukasawa, T., Yoshizaki‐Ogawa, A., Asano, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26099-w · Cited by 88 · see citing works
Interleukin-31: A Novel Diagnostic Marker of Allergic Diseases
Rabenhorst, A., & Hartmann, K. (2014) · Current Allergy and Asthma Reports · doi:10.1007/s11882-014-0423-y · Cited by 85 · see citing works
Increased plasma IL-17, IL-31, and IL-33 levels in chronic spontaneous urticaria
Wei, L., Zhou, Q., Liu, C., Ying, M.-X., & Xu, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-18187-z · Cited by 85 · see citing works
IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity
Takamori, A., Nambu, A., Sato, K., Yamaguchi, S., Matsuda, K., Numata, T., Sugawara, T., Yoshizaki, T., Arae, K., Morita, H., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-25094-4 · Cited by 85 · see citing works
Kunsleben, N., Rüdrich, U., Gehring, M., Novak, N., Kapp, A., & Raap, U. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.106 · Cited by 85 · see citing works
“Another cytokine correlating with disease severity in patients with AD is the pruritogenic IL-31 (Raap et al., 2008; Raap et al., 2012).”
BackgroundSelf-citationEosinophils are a Major Source of Interleukin-31 in Bullous Pemphigoid
Rüdrich, U., Gehring, M., Papakonstantinou, E., Illerhaus, A., Engmann, J., Kapp, A., Hartmann, K., Meyer, N. H., Gibbs, B. F., & Raap, U. (2018) · Acta Dermato Venereologica · doi:10.2340/00015555-2951 · Cited by 82 · see citing works
Self-citationYamamura, K., Uruno, T., Shiraishi, A., Tanaka, Y., Ushijima, M., Nakahara, T., Watanabe, M., Kido‐Nakahara, M., Tsuge, I., Furue, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms13946 · Cited by 82 · see citing works
“In addition, in patients with AD, IL-31 is expressed by cutaneous lymphocyte antigen-positive skin homing CD4 þ T cells 18,20 , and serum IL-31 levels have been shown to correlate with the disease activity 21 .”
Singh, B. B., Jegga, A. G., Shanmukhappa, K. S., Edukulla, R., Khurana, G. H., Medvedovic, M., Dillon, S. R., & Madala, S. K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161877 · Cited by 81 · see citing works
“Serum IL-31 level was found to be significantly elevated in AD patients as compared to healthy controls [31, 32].”
BackgroundNew and emerging treatments for inflammatory itch
Erickson, S., Heul, A. V., & Kim, B. S. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2020.05.028 · Cited by 79 · see citing works
Control of the Physical and Antimicrobial Skin Barrier by an IL-31–IL-1 Signaling Network
Hänel, K. H., Pfaff, C. M., Cornelissen, C. G., Amann, P. M., Marquardt, Y., Czaja, K., Kim, A. L., Lüscher, B., & Baron, J. M. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1402943 · Cited by 76 · see citing works
A Modular View of Cytokine Networks in Atopic Dermatitis
Carmi-Levy, I., Homey, B., & Soumelis, V. (2011) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8239-6 · Cited by 76 · see citing works
Serum IL-31 Levels are Increased in Patients with Cutaneous T-cell Lymphoma
Ohmatsu, H., Sugaya, M., Suga, H., Morimura, S., Miyagaki, T., Kai, H., Kagami, S., Fujita, H., Asano, Y., Tada, Y., et al. (2012) · Acta Dermato Venereologica · doi:10.2340/00015555-1345 · Cited by 75 · see citing works
Kasutani, K., Fujii, E., Ohyama, S., Adachi, H., Hasegawa, M., Kitamura, H., & Yamashita, N. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12823 · Cited by 73 · see citing works
“Serum IL-31 levels also increase in AD and there is a significant correlation with disease severity (Raap et al., 2008; Ezzat et al., 2011).”
BackgroundHuman Th2 but Not Th9 Cells Release IL-31 in a STAT6/NF-κB–Dependent Way
Maier, E., Werner, D., Duschl, A., Bohle, B., & Horejs‐Hoeck, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301836 · Cited by 67 · see citing works
“Although there is convincing evidence that IL-31 induces proinflammatory cytokines, and there is a clear correlation between IL-31 level and disease severity in atopic skin disorders (13, 15, 42, 43), further observations are needed to elucidate the definite role of IL-31 in allergic inflammation.”
BackgroundLee, C., Hong, C., Yu, W.-T., Chuang, H., Huang, S. K., Chen, G., Yoshioka, T., Sakata, M., Liao, W., Ko, Y., et al. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.11047.x · Cited by 68 · see citing works
Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies
Nygaard, U., Vestergaard, C., & Deleuran, M. S. (2017) · Dermatology · doi:10.1159/000484406 · Cited by 67 · see citing works
Hartmann, K., Wagner, N., Rabenhorst, A., Pflanz, L., Leja, S., Förster, A., Gehring, M., Kapp, A., & Raap, U. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.11.008 · Cited by 67 · see citing works
Self-citationIL-31 Serum Protein and Tissue mRNA Levels in Patients with Atopic Dermatitis
Kim, S. J., Kim, H. J., Yang, H. S., Kim, E., Huh, I., & Yang, J.-M. (2011) · Annals of Dermatology · doi:10.5021/ad.2011.23.4.468 · Cited by 66 · see citing works
“In previous study, Raap et al.19 found that serum IL-31 levels were significantly higher in both ADe and ADi patients, without any difference between AD subgroups, and also showed that SCORAD score was significantly correlated with serum IL-31 level in all AD patients.”
ResultGonzales, A. J., Fleck, T. J., Humphrey, W. R., Galvan, B. A., Aleo, M. M., Mahabir, S. P., Tena, J., Greenwood, K. G., & McCall, R. B. (2015) · Veterinary Dermatology · doi:10.1111/vde.12280 · Cited by 66 · see citing works
Chronic Pruritus: Current and Emerging Treatment Options
Pereira, M. P., & Ständer, S. (2017) · Drugs · doi:10.1007/s40265-017-0746-9 · Cited by 66 · see citing works
“Interleukin-31 released by CD4? T cells and T helper-2 cells plays a central role in pruritus transmission in inflammatory pruritic conditions [47] and thus constitutes a relevant target [48].”
BackgroundSelf-citationStänder, S., Raap, U., Weißhaar, E., Schmelz, M., Mettang, T., Handwerker, H. O., & Luger, T. A. (2011) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0387.2011.07585.x · Cited by 64 · see citing works
Self-citationMast cells and basophils in cutaneous immune responses
Otsuka, A., & Kabashima, K. (2014) · Allergy · doi:10.1111/all.12526 · Cited by 63 · see citing works
Pruritus in Autoimmune and Inflammatory Dermatoses
Zeidler, C., Pereira, M. P., Huet, F., Misery, L., Steinbrink, K., & Ständer, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01303 · Cited by 62 · see citing works
“This was surprising, because IL31 levels are increased in other pruritic dermatoses like AD (58) and psoriasis vulgaris (59).”
BackgroundSelf-citation25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways
Bonanno, A., Gangemi, S., Grutta, S. L., Malizia, V., Riccobono, L., Colombo, P., Cibella, F., & Profita, M. (2014) · Mediators of Inflammation · doi:10.1155/2014/520241 · Cited by 60 · see citing works
“Plasma IL-31 concentration was found to be significantly elevated in patients with atopic dermatitis (AD) compared to healthy individuals [18] and positively correlated with disease severity [19].”
BackgroundEndotypes of atopic dermatitis
Fyhrquist, N., Yang, Y., Karisola, P., & Alenius, H. T. (2025) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2025.02.029 · Cited by 63 · see citing works
Oyama, S., Kitamura, H., Kuramochi, T., Higuchi, Y., Matsushita, H., Suzuki, T., Goto, M., Adachi, H., Kasutani, K., Sakamoto, A., et al. (2016) · Experimental Dermatology · doi:10.1111/exd.13236 · Cited by 57 · see citing works
Exploring the Role of Staphylococcus Aureus Toxins in Atopic Dermatitis
Yoshikawa, F. S. Y., de Lima, J. F., Sato, M. N., Ramos, Y. Á. L., Aoki, V., & Orfali, R. L. (2019) · Toxins · doi:10.3390/toxins11060321 · Cited by 58 · see citing works
“IL-31 is a Th2 cytokine associated with AD severity and pruritus [80,81].”
BackgroundMalignancy‐associated pruritus
Rowe, B., & Yosipovitch, G. (2015) · European Journal of Pain · doi:10.1002/ejp.760 · Cited by 56 · see citing works
Altrichter, S., Hawro, T., Hänel, K. H., Czaja, K., Lüscher, B., Maurer, M., Church, M. K., & Baron, J. M. (2014) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.12831 · Cited by 56 · see citing works
Atopic eczema or atopiform dermatitis
Bos, J. D., Brenninkmeijer, E. E. A., Schram, M. E., Middelkamp-Hup, M. A., Spuls, P. I., & Smitt, J. H. S. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.01024.x · Cited by 56 · see citing works
Atopic Dermatitis: Striving for Reliable Biomarkers
Mastraftsi, S., Vrioni, G., Bakakis, M., Nicolaidou, E., Rigopoulos, D., Stratigos, A., & Gregoriou, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11164639 · Cited by 59 · see citing works
Cytokine modulation of atopic itch
Trier, A. M., & Kim, B. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.05.005 · Cited by 55 · see citing works
“Patients with AD have increased cutaneous expression of IL-31 and disease activity has also been found to correlate with serum levels of IL-31 [18,19].”
BackgroundPetra, A. I., Tsilioni, I., Taracanova, A., Katsarou‐Katsari, A., & Theoharides, T. C. (2018) · Allergy and Asthma Proceedings · doi:10.2500/aap.2018.38.4105 · Cited by 54 · see citing works
“Moreover, serum levels of IL-31 were increased and correlated with disease severity in AD.(27,28) In fact, IL-31 was shown to induce dermatitis in mice.”
BackgroundInfluentialInterleukin-31 expression and relation to disease severity in human asthma
Lai, T., Wu, D., Li, W., Chen, M., Yi, Z.-N., Huang, D. A., Jing, Z., Lü, Y., Lv, Q., Li, D., et al. (2016) · Scientific Reports · doi:10.1038/srep22835 · Cited by 52 · see citing works
“IL-31 signals through the heterodimeric receptor IL-31RA and OSMR, and has been linked with the development of atopic dermatitis 21 .”
Staphylococcal α-Toxin Induces a Higher T Cell Proliferation and Interleukin-31 in Atopic Dermatitis
Niebuhr, M., Mamerow, D., Heratizadeh, A., Satzger, I., & Werfel, T. (2011) · International Archives of Allergy and Immunology · doi:10.1159/000323905 · Cited by 50 · see citing works
Self-citation
- Authors
- Raap, U., Wichmann, K., Bruder, M., Ständer, S., Wedi, B., Kapp, A., & Werfel, T.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- University of Münster (DE)
- Corresponding author
- Raap, Ulrike
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 122
- Issue
- 2
- Pages
- 421-423
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2083380164
- Cited by
- 299
- References
- 10
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 15 · 2023: 19 · 2022: 15 · 2021: 24 · 2020: 12 · 2019: 17 · 2018: 26 · 2017: 26 · 2016: 26 · 2015: 21 · 2014: 22 · 2013: 12 · 2012: 11
- FWCI
- 15.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Food Allergy and Anaphylaxis Network
- European Commission
- Astellas Pharma
- Medizinischen Hochschule Hannover
- UCB Pharma
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- atopic dermatitis, IL-31, pruritus, disease severity, cytokines, scratching behavior, NC/Nga mice, T cells, quality of life, antipruritic therapy
- MeSH terms
- Adult, Dermatitis, Atopic, Humans, Interleukins, Middle Aged
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