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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BackgroundInfluential
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Background
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Background
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Background
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Background
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Background
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Anti-Inflammatory Properties of Clindamycin: A Review of Its Use in the Treatment of Acne Vulgaris
Ditre, & Whitney, K. (2011) · Clinical Medicine Insights Dermatology · doi:10.4137/cmd.s5058 · Cited by 12
“5% gel (1) vs. CDP 1.2% (2) vs. BPO 2.5% (3) vs. placebo (4) for 12 weeks 49 n/a n/a 24 (1) vs. (4) ,0.001 45 n/a n/a 27 (1) vs. (4) ,0.001 44 n/a n/a 19 (1) vs. (4) ,0.001 Clindamycin vs. retinoid combinations wolf et al,40 249 Mild-moderate CDP 1% lotion/adaplane gel 0.1% vs. CDP 1% lotion/vehicle for 12 weeks 55 44…”
BackgroundInfluential
Macrophage‐activating lipopeptide‐2 and corticotropin‐releasing hormone stimulate the inflammatory signalling in human sebocytes through activation of stearoyl‐CoA desaturase and fatty acid desaturase 2
Zouboulis, C. C., & Angres, S. (2020) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.17016 · Cited by 12
The Secretion of Inflammatory Cytokines Triggered by TLR2 Through Calcium‐Dependent and Calcium‐Independent Pathways in Keratinocytes
Kim, E.-O., Park, D., Ha, I. J., Bae, S.-E., Lee, M. Y., Yun, M., & Kim, K. (2024) · Mediators of Inflammation · doi:10.1155/mi/8892514 · Cited by 11
Immunohistochemical expression of interleukin 1 beta in papule biopsies from patients with acne vulgaris
Le, T. V. T., Anh, L. V., Tran, G. H., Hung, T. Q., Trung, V. T., & Vuong, N. L. (2022) · Dermatology Reports · doi:10.4081/dr.2022.9444 · Cited by 11
Acne vulgaris is associated with intensive pubertal development and altitude of residence—a cross-sectional population-based study on 6,200 boys
Robeva, R. N., Assyov, Y. S., Tomova, A., & Kumanov, P. (2012) · European Journal of Pediatrics · doi:10.1007/s00431-012-1907-1 · Cited by 11
Acne Maintenance Therapy
Zane, L. T. (2006) · Archives of Dermatology · doi:10.1001/archderm.142.5.638 · Cited by 11
The Genetics of Acne
Steensel, M. A. M. V. (2025) · Annals of Human Genetics · doi:10.1111/ahg.70014 · Cited by 11
“Higher levels of stearoylcarnitine are associated with a decreased number of CD4 + T-cells (Qian et al. 2021), the exact cell type that was long ago observed in early acne lesions (Jeremy et al. 2003).”
Acne Assessment and Grading: Challenges and Opportunity
Paluri, K. V., & Gupta, A. (2023) · International Conference on Computational Systems and Communication (ICCSC) · doi:10.1109/iccsc56913.2023.10143016 · Cited by 10
“it is present mostly on the face, forehead, neck, upper back, shoulders, and chest [7].”
Background
Acne vulgaris - review on pathogenesis and treatment
Żmuda, B., Żuberek, M., Ślusarczyk, D., Pisera, P., Kiełkowicz, A., Popińska, Z., Pactwa, F., & Jakubowska, W. (2024) · Journal of Education Health and Sport · doi:10.12775/jehs.2024.51.004 · Cited by 10
“There is proven link between increased activity of Interleukin-1 and keratinocyte hyperproliferation[14].”
Background
Is the current model for acne pathogenesis backwards?
Metiko, B., Brooks, K., Burkhart, C. G., Burkhart, C. N., & Morrell, D. S. (2015) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2015.01.041 · Cited by 10
Environmental, inflammatory, and anti‐inflammatory squad in acne vulgaris pathogenesis: AhR, IL‐36, and IL‐38
Elesawy, F. M., Mohammed, S. A., Nasar, E. N. Z., Mostafa, S. H., & Elhabak, D. M. (2021) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14542 · Cited by 10
Epidemiology and Management of Acne in Adult Women
Fisk, W. A., Lev‐Tov, H. A., & Sivamani, R. K. (2014) · Current Dermatology Reports · doi:10.1007/s13671-014-0071-4 · Cited by 10
Benzoyl peroxide and adapalene fixed combination: a novel agent for acne
Layton, A., & Eady, E. A. (2009) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2009.09531.x · Cited by 10
The Role of Probiotics in Acne and Rosacea
Porubsky, C. F., Glass, A. B., Comeau, V., Buckley, C. D., Goodman, M. B., & Kober, M.-M. (2018) · InTech eBooks · doi:10.5772/intechopen.79044 · Cited by 10
“In the above study, an increased level of IL-1-alpha was observed in both early lesional skin and uninvolved skin of acne patients in comparison with the control group [39].”
BackgroundResultInfluential
Highly Efficient and Biocompatible nanoparticle-based Photosensitizer for Treatment of Acne Vulgaris
Wang, P., Tang, H. M., & Zhang, P. (2018) · Nanomedicine · doi:10.2217/nnm-2018-0125 · Cited by 10
Involvement of Pattern Recognition Receptors in the Direct Influence of Bacterial Components and Standard Antiacne Compounds on Human Sebaceous Gland Cells
Zouboulis, C. C., Oeff, M. K., Hiroi, N., Makrantonaki, E., & Bornstein, S. R. (2021) · Skin Pharmacology and Physiology · doi:10.1159/000513259 · Cited by 10
Isolation and Identification of Lactic Acid Bacteria Inhibiting the Proliferation of Propionibacterium acnes and Staphylococcus epidermidis
Kang, M., Oh, H.-J., Lee, H., & Oh, J. (2009) · Journal of Bacteriology and Virology · doi:10.4167/jbv.2009.39.1.11 · Cited by 10
Genetics of Hidradenitis Suppurativa
von der Werth, J., Wood, P., Irvine, A. D., & McLean, W. H. I. (2006) · Springer eBooks · doi:10.1007/978-3-540-33101-8_10 · Cited by 10
“The cytokines involved, such as IL-1, IL-10, IL-6 and TNF, have roles in the development of epidermal appendages, hyperproliferation and cornification of epidermal cells and initiation of immune signalling [6, 14, 15, 17, 24, 29, 38].”
Background
Phytochemicals as emerging therapeutics for acne vulgaris: a comprehensive review
El‐Shiekh, R. A., Merghany, R. M., Fayez, N., Hassan, M., Bakr, A. F., Eid, O., Ali, D. E., & Sweilam, S. H. (2025) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-025-00842-2 · Cited by 9
“Inside the microcomedone, macrophages, CD3, and CD4 cells are also detected as well as activation of vascular adhesion molecules such as E-selectin and integrin [30].”
A Call for Gender Identity Data Collection in iPLEDGE and Increasing the Number of Isotretinoin Prescribers Among Transgender Health Providers
Singer, S. B., & Keuroghlian, A. S. (2020) · LGBT Health · doi:10.1089/lgbt.2019.0313 · Cited by 9
Importancia de la inmunidad innata en el acné
Moreno‐Arrones, Ó. M., & Boixeda, P. (2016) · Actas Dermo-Sifiliográficas · doi:10.1016/j.ad.2016.07.005 · Cited by 9
Innate immunity in the pathogenesis of acne vulgaris
Krishna, S. M., Kim, C., & Kim, J. J. (2011) · CRC Press eBooks · doi:10.3109/9781616310097-4 · Cited by 11
In vivo study of orange peel fermentation and improvement of androgen overproduction causing acne
Yuan, Y., Zhou, J., Zhang, N., Xing, X., Zhao, L., & Zhou, F. (2023) · Food Bioscience · doi:10.1016/j.fbio.2023.103124 · Cited by 8
Acupuncture: A therapeutic approach against acne
Chun‐Yan, C., Xu, G., Yan‐yan, S., Xu, M., & Liu, P. (2021) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14487 · Cited by 8
Hyperspectral assessment of acne skin exposed to intense pulsed light (IPL) intense pulsed light in acne treatment
Zdrada, J., Stolecka‐Warzecha, A., Odrzywołek, W., Deda, A., Błońska‐Fajfrowska, B., & Wilczyński, S. (2023) · Skin Research and Technology · doi:10.1111/srt.13338 · Cited by 8
vB_CacS-HV1 as a Novel Pahexavirus Bacteriophage with Lytic and Anti-Biofilm Potential against Cutibacterium acnes
Xu, L., Ding, W., Li, Z., Yan, Y. L., Tong, Y., Xu, J., & Li, M. (2024) · Microorganisms · doi:10.3390/microorganisms12081566 · Cited by 8
“…research has indicated that the proliferation of C. acnes can reduce skin microbiota diversity and enhance keratinocyte differentiation, the disruption of sebaceous gland activity, and local inflammation and immune system activation, which are the four main factors of acne pathogenesis [15–19].”
Background
Anti-inflammatory properties of a new undecyl-rhamnoside (APRC11) against P. acnes
Isard, O., Lévêque, M., Knol, A., Ariès, M.-F., Khammari, A., Nguyen, J., Castex‐Rizzi, N., & Dréno, B. (2011) · Archives of Dermatological Research · doi:10.1007/s00403-011-1147-7 · Cited by 8
The Effects of Myrtle (Myrtus communis) and Clindamycin Topical Solution in the Treatment of Mild to Moderate Acne Vulgaris: A Comparative Split-Face Study
Salmanian, M., Shirbeigi, L., Hashem-Dabaghian, F., Mansouri, P., Azizkhani, M., Alavi, S., & Ghobadi, A. (2020) · Journal of pharmacopuncture · doi:10.3831/kpi.2020.23.4.220 · Cited by 8
“Three free radicals (hydroxyl, superoxide and nitrous oxide) are responsible for the occurrence of irritation during the acne infection; therefore, the use of antioxidant and antiinflammatory agents has been considered along with usual medication on the treatment of acne vulgaris [15, 25, 26].”
Background
Cosmeceutical Aptitudes of Azelaic Acid
Singh, S. K., Chaubey, S., Bansal, A. K., Kaur, G., & Malik, D. S. (2021) · Current Drug Research Reviews · doi:10.2174/2589977513666210526122909 · Cited by 8
Efficacy, tolerability, and safety of montelukast versus finasteride for the treatment of moderate acne in women: A prospective, randomized, single‐blinded, active‐controlled trial
Rokni, G. R., Mohammadnezhad, F., Saeedi, M., Shadi, S., Sharma, A., Sandhu, S., Gupta, A., & Goldust, M. (2021) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14462 · Cited by 8
Clindamycin 1% Nano-emulsion Gel Formulation for the Treatment of Acne Vulgaris: Results of a Randomized, Active Controlled, Multicentre, Phase IV Clinical Trial
Sanmukhani, J. (2014) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2014/9111.4769 · Cited by 8
“Until recently follicular epidermal hyperproliferation with subsequent plugging of the follicles (comedones) was considered to be the earliest event in the development of acne and closed comedones were regarded as the precursors of inflammatory lesions [6,7].”
Background
EFFECTS OF ALPHA-MANGOSTIN AND CITRONELLA OIL AGAINST ACNE CAUSING BACTERIA
TANNGOEN, P., Lamlertthon, S., & Tiyaboonchai, W. (2019) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2019v11i6.32927 · Cited by 8
“acnes proliferation, it can induce the production of inflammatory mediators, which are accountable for the inflammation, redness, and pain associated with acne breakouts [7, 8].”
Background
Chitosan application in cosmetics and dermatology – Antimicrobial and prebiotic potential to control human microbiome
Delic, M., Butorova, I., & Николаевич, К. А. (2025) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2025.09.014 · Cited by 12
Recent therapeutic developments for acne
Thielitz, A., & Gollnick, H. P. M. (2013) · Expert Review of Dermatology · doi:10.1586/edm.12.70 · Cited by 7
Solodyn and Updates on Topical and Oral Therapies for Acne
Bowe, W. P., Glick, J. B., & Shalita, A. R. (2012) · Current Dermatology Reports · doi:10.1007/s13671-012-0014-x · Cited by 7
“[6] suggest inflammation may precede keratinization and noted the presence of elevated levels of proinflammatory cytokine interleukin (IL)-1, even prior to follicular plugging.”
Background
Mangosteen (Garcinia mangostana Linn.): Role in Prevention of Skin Disorders
Upaganlawar, A., & Badole, S. L. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-167-7_42 · Cited by 7
A pilot study on serum lactoferrin in patients with mild versus severe acne in correlation with disease duration
Sharara, M. A., Diab, H. M., & Reda, A. E. R. (2019) · Journal of the Egyptian Womenʼs Dermatologic Society · doi:10.4103/jewd.jewd_35_19 · Cited by 7
A Consensus on Acne Management Focused on Specific Patient Features
Lynde, C. W., Tan, J. K. L., Andriessen, A., Barankin, B., Dutil, M., Gilbert, M. J., Hong, C.-H., Humphrey, S. D., Rochette, L., Toole, J., et al. (2014) · Journal of Cutaneous Medicine and Surgery · doi:10.2310/7750.2013.13154 · Cited by 8

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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