Cited by 541Acne and Rosacea Treatments and EffectsDermatology and Skin DiseasesPsoriasis: Treatment and Pathogenesis

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Inflammatory Events Are Involved in Acne Lesion Initiation

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Jeremy, Anthony H.T., Holland, Diana B., Roberts, Susan G., Thomson, Kathryn F., Cunliffe, William J.·2003·Journal of Investigative Dermatology

DOI 10.1046/j.1523-1747.2003.12321.x

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Abstract

The earliest subclinical acne "lesion" is a microcomedone, of which hyperproliferation of the follicular epithelium is a characteristic feature. Inflammatory cells have been observed at the periphery of these "lesions". This study investigated whether inflammatory events occur pre or post hyperproliferative changes. Cellular, vascular, and proliferative markers were examined by immunohistochemical techniques on biopsies of clinically normal follicles from uninvolved skin and early inflamed lesions from acne patients. Control follicles were obtained from non-acne subjects. Follicles from uninvolved skin exhibited no microcomedonal features. Proliferation in the epithelium was comparable to controls and was significantly lower than in inflamed lesions. Numbers of CD3+, CD4+ T cells were elevated in the perifollicular and papillary dermis although levels were not equivalent to those in papules. The number of macrophages was also greatly increased and similar to those in papules. There were no changes in blood vessel numbers or vascular intercellular adhesion molecule 1 expression but E-selectin expression was increased to levels found in papules and vascular adhesion molecule 1 levels were upregulated. Levels of the pro-inflammatory cytokine interleukin-1 were also upregulated perifollicularly. Moreover, aberrant integrin expression was demonstrated in the epidermis around these uninvolved follicles and inflamed lesions whereas the basement membrane was still intact. These results provide novel evidence for vascular endothelial cell activation and involvement of inflammatory responses in the very earliest stages of acne lesion development.

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“C . acne activates inflammatory pathways in HaCaT keratinocytes, inducing the release of inflammatory cytokines such as interleukin (IL)-1 β , IL-8, and tumor necrosis factor (TNF)- α , which attract macrophages to the affected area via chemotaxis [7].”
Acne
Østergaard, C. E. S., Bertelsen, T., Lomholt, H. B., Kofoed, K., & Gyldenløve, M. (2025) · Ugeskrift for Læger · doi:10.61409/v09240660 · Cited by 2
DABNet: Hybrid Acne Classification Approach with Attention-Based Transfer Learning using Bayesian Optimization
Paluri, K. V., Gupta, A., & Nain, G. (2025) · International Conference on Emerging Systems and Intelligent Computing (ESIC) · doi:10.1109/esic64052.2025.10962593 · Cited by 2
“It typically manifests as pimples, blackheads, whiteheads, papules, pustules, or cysts on the face, chest, back, and shoulders [3, 4].”
The Effect of Forkhead Box Class O1, Mammalian Target of Rapamycin Complex 1, Survivin, and Interleukin-17 on the Degree of Acne Vulgaris Based on Serum Levels
Hanum, S. Y. M., Nasrul, E., Jusuf, N. K., & Yerizel, E. (2020) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2020.3522 · Cited by 2
“Inflammatory cells (CD3 and CD4 T-cells) are also found to be increased in microcutaneous lesions with a number that is not much different when compared with pustular lesions [24].”
Result
A Review on Antimicrobial Activity of Tarunyapidikahara Lepa Ingredients
Sharma, U. K., Sharma, S., Kumari, P., Mitra, S., Yadav, Y., & Sharma, K. C. (2022) · Scholars International Journal of Traditional and Complementary Medicine · doi:10.36348/sijtcm.2022.v05i03.002 · Cited by 2
“Retention-proliferation hyperkeratosis first form microcomedone, which further grow and convert into comedone and this comedone further develop and form acne [9, 10].”
Background
l-Ascorbyl-2-phosphate attenuates NF-κB signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion
Ikeno, H., Apel, M., Zouboulis, C. C., Luger, T. A., & Böhm, M. (2015) · Archives of Dermatological Research · doi:10.1007/s00403-015-1565-z · Cited by 2
“Moreover, the antioxidant glutathione was recently found to be lower in the stratum corneum of patients with acne than in healthy subjects [17].”
Background
A Comparison of Red and Blue Light Emitting Diode Lights in Photodynamic Therapy for the Treatment of Acne Vulgaris
Park, H. Y., Yun, S. J., Kim, S., Lee, S. C., Won, Y. H., & Lee, J. B. (2010) · Linchuang pifuke zazhi · Cited by 2
Nanotechnology Applications in Dermatology
Schairer, D. O., Chouake, M., Nasir, M., & Friedman, A. (2013) · CRC Press eBooks · doi:10.1201/b15642-3 · Cited by 2
Efficacy of Dapsone 5% gel in treatment of Acne vulgaris
Jawade, S. A., & Singh, A. (2016) · International Journal of Research in Dermatology · doi:10.18203/issn.2455-4529.intjresdermatol20163502 · Cited by 2
Effect of Dapsone Gel 7.5% Compared to Tazarotene Gel 0.1% for Treatment of Acne Vulgaris
Ibrahim, S., Labeeb, Z., & Amer, A. (2019) · Zagazig University Medical Journal · doi:10.21608/zumj.2019.7618.10400 · Cited by 2
“Antibacterial activities are similar to sulfones [6].”
Acne Clinic: Morphogenesis
Plewig, G., Melnik, B. C., & Chen, W. (2019) · Springer eBooks · doi:10.1007/978-3-319-49274-2_4 · Cited by 2
Systemic antibiotics therapy of acne: certain controversies
Araviyskaya, Y. R., & Sokolovsky, Y. V. (2013) · Vestnik dermatologii i venerologii · doi:10.25208/vdv629 · Cited by 2
“(2003) показали, что такая реакция индуцируется провоспалительным цитокином интерлейкином-1α в ответ на дефицит линолевой кислоты и нарушение барьерных свойств кожи [4].”
Comedogenesis
Heughebaert, C. (2011) · CRC Press eBooks · doi:10.3109/9781616310097-5 · Cited by 2
Calprotectin may be positively associated with the severity of acne vulgaris
Al-tameemi, S., Abid, Z., Chen, W., Alshammri, F., & Abid, H. A. (2022) · Baghdad Journal of Biochemistry and Applied Biological Sciences · doi:10.47419/bjbabs.v3i02.124 · Cited by 2
An Overview About Acne Vulgaris
Mustafa, S. A. G. (2022) · Journal of Pharmaceutical Negative Results · doi:10.47750/pnr.2022.13.s07.551 · Cited by 2
Infections of the Facial Skin and Scalp
Banki, A., & Castiglione, F. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-28945-0.00022-3 · Cited by 2
Protective effect of rhIL-1β on pancreatic islets of alloxan-induced diabetic rats
Wu, L.-P. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i22.3353 · Cited by 2
Acne
Melnik, B. C. (2011) · Wiley eBooks · doi:10.1002/9781444345384.ch79 · Cited by 2
An Open-label, Prospective, Comparative, Double-arm Clinical Trial to Evaluate the Safety and Effectiveness of Minocycline Extended-release Formulation Compared with Minocycline Immediate-release Formulation in the Management of Patients with Papulopustular Acne
Pande, S., Deshmukh, G. A., Dhoot, D. S., & Andhorikar, N. (2020) · Indian Journal of Drugs in Dermatology · doi:10.4103/ijdd.ijdd_47_20 · Cited by 1
Nature’s Remedy: A Comprehensive Review Exploring Herbal Treatments and Natural Approaches for Preventing Acne Vulgaris
Shingari, M., Sharma, A., & Mittal, V. (2025) · Recent Advances in Anti-Infective Drug Discovery · doi:10.2174/0127724344345143250709035643 · Cited by 1
Exploring the Therapeutic Potential of Fluorouracil in Addressing Skin Aging and Diseases
Liang, Y., Li, J., Su, X., Zhuang, J., Chen, Q., Zhang, Z., Wei, Q., & Hu, J. (2025) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000012050 · Cited by 1
Acne tarda: Recommendations for classification, treatment and care as a result of an expert discussion
Augustin, M., Dirschka, T., Gerber, P. A., Kerscher, M. J., Kirsten, N., & Ochsendorf, F. R. (2025) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/ddg.15913 · Cited by 1
“46,47 In patients with acne tarda, sebor-rhea and increased androgen secretion were found to be comparable to acne vulgaris.”
Evaluation of serum inflammatory markers in acne patients treated with systemic isotretinoin or doxycycline
Günegül, N. E., Örenay, Ö. M., & Karaosmanoğlu, N. (2025) · Archives of Dermatological Research · doi:10.1007/s00403-025-04478-3 · Cited by 1
“Evidence suggests that inflammation is pres - ent even in microcomedones, which are the earliest lesions in acne pathology [13].”
Antimicrobial Blue Light and Acne Vulgaris: Unraveling Therapeutic Insights
Diogo, M. L. G. (2026) · Springer eBooks · doi:10.1007/978-3-031-55858-0_131-1 · Cited by 1
Exposome involvement in the development of acne vulgaris
Grafanaki, K., Bakoli, D., Maniatis, A., & Zouboulis, C. C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1779036 · Cited by 1
Pathogenese und Therapie der Akne: Aktuelle Aspekte
Ochsendorf, F. R. (2007) · Aktuelle Dermatologie · doi:10.1055/s-2007-966124 · Cited by 1
The effect of probiotics on skin
Chang, J., Duizendstra, A. A., Jansen, R., Jimena, A., Gutierrez, P., Zhao, T. R., Weijers, C., Lommen, W., Ultee, J., & Boog, M. (2014) · Cited by 1
Acne
Treloar, V. (2009) · CRC Press eBooks · doi:10.1201/9781420067637.ch20 · Cited by 1
Effect of systemic isotretinoin use on neutrophil/lymphocyte ratio in acne patients: A retrospective study
Akça, H. M. (2022) · Journal of Contemporary Medicine · doi:10.16899/jcm.1158798 · Cited by 1
Role of dermatocosmetics in treatment strategy for acne patients
Kruglova, L. S., Gryazeva, N. V., & Verbovaya, E. D. (2022) · Medical alphabet · doi:10.33667/2078-5631-2022-27-67-72 · Cited by 1
Research Progress of Skin Barrier and Acne
(2023) · International Journal of Health and Pharmaceutical Medicine · doi:10.38007/ijhpm.2023.040111 · Cited by 1

Authors: Jeremy, A. H. T., Holland, D. B., Roberts, S. G., Thomson, K. F., & Cunliffe, W. J.
Affiliations: Leeds General Infirmary (GB)
Corresponding author: Holland, Diana B.
ORCID: Cunliffe, William J.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2003-07
Volume: 121
Issue: 1
Pages: 20-27
ISSN: 0022-202X (ISSN-L)
DOI: 10.1046/j.1523-1747.2003.12321.x
OpenAlex: W2062768474
Cited by: 541
References: 34
Citations by year: 2026: 13 · 2025: 30 · 2024: 52 · 2023: 28 · 2022: 20 · 2021: 28 · 2020: 26 · 2019: 32 · 2018: 29 · 2017: 24 · 2016: 23 · 2015: 19 · 2014: 35 · 2013: 27 · 2012: 17
FWCI: 16.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4537 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: acne, microcomedones, inflammation, T cells, macrophages, endothelial activation, E-selectin, VCAM-1, interleukin-1, integrins, basement membrane, follicular epithelium, vascular adhesion molecules
MeSH terms: CD68 Molecule, Acne Vulgaris, Adolescent, Adult, Blood Vessels, Cell Differentiation, Cell Division, HLA-DR Antigens, Humans, Immunohistochemistry, Immunologic Memory, Interleukin-1, Laminin, Langerhans Cells, Macrophages, Neutrophils, Antigens, Differentiation, Myelomonocytic, Biomarkers, CD4-Positive T-Lymphocytes, Keratinocytes, Antigens, CD, CD3 Complex, Receptors, Interleukin-1, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Hair Follicle, Antigens, CD1, Collagen Type IV, Integrin alpha6, Receptors, Interleukin-1 Type II

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Inflammatory Events Are Involved in Acne Lesion Initiation

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