Table 3.
Interleukins involved in dermatological diseases, important associated comorbidities, and relevant experimental or approved therapeutics
| Interleukin | Important dermatological conditions | Important co-morbidities | Relevant therapeutics | References |
|---|---|---|---|---|
|
IL-1α/β IL-RA |
Hereditary systemic autoinflammatory diseasesa Systemic inflammatory diseasesb Hidradenitis suppurativa Pustular psoriasis Neutrophilic dermatoses Urticarial vasculitis Kawasaki disease Erdheim–Chester disease |
Diabetes Cardiac remodeling Gout RA Osteoarthritis GVHD Dry eye disease |
Rilonacept is an interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) cytokine trap indicated for cryopyrin-associated periodic syndromes, familial cold autoinflammatory syndrome and Muckle–Wells syndrome, deficiency of IL-1 receptor antagonist, and recurrent pericarditis Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody indicated for treatment of autoinflammatory periodic fever syndromes Anakinra is a recombinant, nonglycosylated form of IL-1RA indicated for rheumatoid arthritis, cryopyrin-associated periodic syndromes (CAPS), and deficiency of interleukin-1 receptor antagonist (DIRA) |
[113–118] |
| IL-2 |
Alopecia areata Malignant melanoma |
Aldesleukin is a recombinant IL-2 protein therapy approved for use in patients with stage IV melanoma | [119, 120] | |
| IL-4 |
Atopic dermatitis Scleroderma Bullous pemphigoid |
Atopic comorbidities | Dupilumab, an FDA approved anti-IL-4Rα monoclonal antibody for treatment of patients with atopic dermatitis or asthma | [70, 121–124] |
| IL-5 |
Atopic dermatitis Hypereosinophilic syndrome |
Asthma EoE Eosinophilic granulomatosis with polyangiitis Nasal polyposis |
Benralizumab, mepolizumab, and reslizumab are 3 FDA-approved anti-IL-5 antibodies for treatment of adult patients with severe eosinophilic asthma | [125–127] |
| IL-6 |
Psoriasis (–) Pustular psoriasis Hidradenitis suppurativa Wound Healing |
RA Psoriatic Arthritis (–) Cardiovascular disease Depression Diabetes |
Tocilizumab, monoclonal antibody against IL-6R, indicated for RA, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, cytokine release syndrome Siltuximab, monoclonal antibody against IL-6, indicated for multicentric Castleman’s disease |
[26, 31, 128–133] |
| IL-7 |
CTCL (elevated levels) Generalized verrucosis and HPV-3 susceptibility (inherited IL-7 deficiency) |
T-cell acute lymphoblastic leukemia Sjögren’s syndrome Multiple sclerosis |
Safety of GSK2618960, an experimental anti-IL-7R antibody, has been assessed in healthy subjects (NCT02293161) RN168, an experimental anti-IL-7R antibody, is being assessed in patients with type I diabetes (NCT02038764) |
[134–140] |
| IL-8 |
Psoriasis Pyoderma gangrenosum |
IBD Ovarian cancer |
BMS-986253 is an experimental anti-IL-8 monoclonal antibody being assessed in patients with incurable metastatic or unresectable solid tumors (NCT02536469) | [32, 33, 141–143] |
| IL-9 |
Atopic dermatitis Allergic contact dermatitis Mycosis fungoides Important defense mechanism against Candida |
[75, 144–147] | ||
| IL-10 |
SLE Pemphigus vulgaris Bullous pemphigoid Alopecia areata Psoriasis Atopic dermatitis Allergic contact dermatitis Melanoma BCC/SCC Cutaneous lymphomas Hypertrophic scarring |
Important in viral diseases: HIV, EBV, Herpesviruses, CMV, Poxviruses Leishmaniasis Leprosy Systemic sclerosis |
SCH708980, a monoclonal anti-IL-10 antibody being assessed as an anti-immunosuppressive agent in visceral leishmaniasis (NCT01437020) | [148, 149] |
| IL-11 |
Psoriasis Atopic dermatitis (skin remodeling) |
Cardiovascular fibrosis | [34, 76, 150] | |
| IL-12 |
Psoriasis Atopic dermatitis Photocarcinogenesis |
Important in protection against infections and allergens | Ustekinumab, an anti-IL-12/23 antibody is indicated for moderate-to-severe plaque psoriasis, active psoriatic arthritis, moderate-to-severe Crohn’s disease, and ulcerative colitis | [36, 151–154] |
| IL-13 |
Atopic dermatitis Behçet’s disease Systemic sclerosis Localized scleroderma |
Dupilumab, see above Lebrikizumab, an experimental anti-IL-13 monoclonal antibody for treatment of atopic dermatitis (NCT03443024) or asthma (NCT02104674) Tralokinumab, anti-IL-13 antibody for treatment of patients with atopic dermatitis (NCT03131648 and NCT03160885) or asthma (NCT02161757 and NCT02194699). It has received regulatory approval by Health Canada |
[83, 155–162] | |
| IL-14 |
Sjögren’s syndrome SLE |
[163, 164] | ||
| IL-15 |
Vitiligo Mycosis fungoides |
RA Sarcoidosis IBD Transplant rejection Hematologic malignancies Infections |
IL-15 superagonist complex N-803 is an experimental treatment being assessed in BCG-unresponsive non-muscle invasive bladder cancer patients (NCT03022825) | [165–168] |
| IL-16 |
Cutaneous T-cell lymphoma Systemic sclerosis SLE Bullous pemphigoid |
HIV/immune reconstitution syndrome | [169–173] | |
| IL-17 |
Psoriasis Psoriatic arthritis Ankylosing spondylitis Tumor progression |
Asthma IBD |
Secukinumab and ixekizumab (IL-17A antibodies) and brodalumab (IL-17RA antibody) Bimekizumab, a monoclonal antibody that targets both IL-17A and IL-17F that was assessed in clinical trials in patients with plaque psoriasis (NCT03536884). It is approved by the EMA, and pending approval by the FDA and Health Canada Sonelokimab is an IL-17A/17F nanobody which neutralizes both IL-17A and IL-17F, and is currently being assessed in patients with plaque psoriasis (NCT03384745) |
[39, 40, 43, 174–178] |
| IL-18 |
Lupus Hemophagocytic syndrome |
IBD CVD |
GSK1070806, an experimental monoclonal antibody against IL-18 (NCT03522662) | [179–183] |
| IL-19 |
Psoriasis Atopic dermatitis |
[46, 184] | ||
| IL-20 | Psoriasis |
RA PsA |
[47, 49] | |
| IL-21 |
SLE Psoriasis Atopic dermatitis Alopecia areata Melanoma (anti-tumorigenic role) |
RA IBD Colon cancer |
[50, 185–192] | |
| IL-22 |
Psoriasis Atopic dermatitis Contact dermatitis Scleroderma CTCL Squamous cell carcinoma |
Multiple sclerosis RA |
Fezakinumab, a monoclonal anti-IL-22 antibody being assessed in atopic dermatitis (NCT01941537) | [51, 52, 77, 193–200] |
| IL-23 | Psoriasis |
Crohn’s disease RA PsA |
Ustekinumab, see above Guselkumab, risankizumab, tildrakizumab |
[35, 90, 201–203] |
| IL-24 |
Psoriasis Contact dermatitis Atopic dermatitis |
IBD (suppresses mucosal inflammation) | [48, 54, 204–206] | |
| IL-25 | Psoriasis | Asthma | [55, 207, 208] | |
| IL-26 |
Hidradenitis suppurativa Psoriasis Behçet’s disease |
RA Crohn’s disease Asthma COPD |
[56, 209–215] | |
| IL-27 |
Psoriasis Systemic sclerosis |
COPD Breast cancer Sjögren's syndrome Rheumatoid Arthritis |
[58, 216–220] | |
| IL-28 | SLE |
Sepsis HCV clearance Hashimoto’s thyroiditis |
[221–224] | |
| IL-29 |
SLE Psoriasis Atopic dermatitis Systemic sclerosis |
RA Osteoarthritis Uveitis Sjögren’s syndrome Hashimoto’s thyroiditis |
Peginterferon Lambda-1A or IL-29 is being assessed in clinical trials for treatment of patients with COVID-19 (NCT04354259) or hepatitis C (NCT01866930) | [62, 224–231] |
| IL-30 | Psoriasis |
Breast cancer Prostate cancer |
[59, 232, 233] | |
| IL-31 | Chronic pruritic skin disorders |
Allergic asthma and rhinitis IBD Osteoporosis |
[234] | |
| IL-32 |
Psoriasis Atopic dermatitis |
Grave’s disease RA Pulmonary arterial hypertension COPD |
[64, 235–239] | |
| IL-33 |
Psoriasis Atopic dermatitis Allergic contact dermatitis Vitiligo Chronic spontaneous urticaria |
Allergic rhinitis Asthma RA Ulcerative colitis |
Itepekimab, experimental monoclonal antibody against IL-33 in COPD (NCT04751487) | [60, 240–247] |
| IL-34 |
SLE Psoriasis |
RA Sjögren’s syndrome IBD Nonalcoholic fatty liver disease Lung cancer PsA |
[65, 248–253] | |
| IL-35 | Systemic sclerosis |
Sjögren's syndrome MS |
[254–256] | |
| IL-36 |
Psoriasis SLE AD |
RA PsA UC Sjögren’s syndrome |
Imsidolimab, a monoclonal antibody against IL-36R; hidradenitis suppurativa (NCT04856930), acneiform eruptions (NCT04697069), ichthyosis (NCT04697056) | [16, 17, 23, 257–261] |
| IL-37 |
Psoriasis SLE |
Ankylosing spondylitis Graves’ disease Guillain-Barré syndrome RA |
[66, 262–266] | |
| IL-38 | Psoriasis |
RA Idiopathic pulmonary lung fibrosis |
[18, 65, 67, 267, 268] | |
| IL-39 |
Neuromyelitis optica spectrum disorders ST-segment elevation myocardial infarction |
[269, 270] |
AD, atopic dermatitis; BCC, basal cell carcinoma; COPD, chronic obstructive pulmonary disease; CTCL, cutaneous T-cell lymphoma; CVD, cardiovascular disease; GVHD, graft-versus-host-disease; IBD, irritable bowel syndrome; MS, multiple sclerosis; NTK, natural killer T; PsA, psoriatic arthritis; SCC, squamous cell carcinoma; SLE, systemic lupus erythematosus; UC, ulcerative colitis
aHereditary systemic autoinflammatory diseases: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), TNF receptor-associated periodic syndrome (TRAPS), hyper-IgD syndrome (HIDS), periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA), deficiency of interleukin-1 (IL-1) receptor antagonist (DIRA)
bSystemic inflammatory diseases: Systemic juvenile idiopathic arthritis, Adult-onset Still’s disease, Schnitzler syndrome, Behçet’s disease, PFAPA, synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome, macrophage activation syndrome