The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha.
Inflammation plays a major role in the induction and progression of several skin diseases. Overexpression of the major epidermal proinflammatory cytokines interleukin (IL) 1 alpha (IL-1α) and 1 beta (IL-1β) is positively correlated with symptom exacerbation and disease progression in psoriasis, atopic dermatitis, neutrophilic dermatoses, skin phototoxicity, and skin cancer. IL-1β and the interleukin-1 receptor I (IL-1RI) have been used as a therapeutic target for some autoinflammatory skin diseases; yet, their system-wide effects limit their clinical usage. Based on the local effects of extracellular IL-1α and its precursor, pro-IL-1α, we hypothesize that this isoform is a promising drug target for the treatment and prevention of many skin diseases. This review provides an overview on IL-1α and IL-β functions, and their contribution to inflammatory and malignant skin diseases. We also discuss the current treatment regimens, and ongoing clinical trials, demonstrating the potential of targeting IL-1α, and not IL-1β, as a more effective strategy to prevent or treat the onset and progression of various skin diseases.
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, 32306.|Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306.
Mayassa J
MJ
Bou-Dargham
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, 32306.|Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306.|Department of Chemistry and Biochemistry, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Zahraa I
ZI
Khamis
Dermatology Associates of Tallahassee and Division of Dermatology, Florida State University College of Medicine, Tallahassee, FL, 32308.
Armand B
AB
Cognetta
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, 32306.|Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, 32306.
Qing-Xiang Amy
QA
Sang
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology / Q000627:therapeutic use; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D058990:Molecular Targeted Therapy; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012871:Skin Diseases / Q000188:drug therapy* / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept
inflammation; interleukin-1; keratinocytes; skin diseases; squamous cell carcinoma