96 SKIN CARE
in seven trials it had no significant effect on ones that were not inflamed.7
If the primary
initiator were infection, one might expect antibiotics to be more effective in the earliest lesions, before the organism had gained a foothold.
Or is it sebum overproduction? The possibility that acne is primarily the result of a metabolic disorder of sebaceous glands, not of infection, has been supported by genetic studies. Susceptibility to developing acne has been found to be strongly inherited,16
and
variations in genes involved in sebaceous gland function shown to be linked to the condition.17 Sebum is a holocrine secretion formed by
disintegration of glandular cells, and accounts for about 90% of skin surface lipids. It has functions in anti-microbial defence, epidermal water retention, and innate immune responses. Its composition is very different from the lipids of epidermal origin. The most striking difference is the presence of squalene and wax esters, epidermal lipids being composed mostly of cholesterol (35%), fatty acids (15%), and ceramides (45%).18,19
Sebum is unusual in
containing sapienic and sebaleic acids, the latter of which is produced only by sebocytes.20 Sebum secretion rate varies widely, and has
been shown by a study of twins to be strongly genetically determined.21
Acne sufferers have
higher average secretion rates than non-sufferers, a difference that develops during puberty, when sebum secretion increases in those who develop acne but not in those who do not.22
The severity
of acne in sufferers is positively correlated with the rate of secretion.23-25
Consistent with this
is the fact that while isotretinoin reduces both secretion rate and acne severity, androgens have the opposite effects.26
Or is it squalene peroxides? While the notion that overproduction of sebum might lead to acne by physically blocking follicular ducts is plausible, the association might not be that simple, as high secretion rates are accompanied by changes in lipid composition. Sebum composition in acne sufferers differs from that in non-sufferers.
A B
specific property of UVA radiation, irradiation with UVB having almost no effect on squalene, and that it occurs even at sub-erythmogenic doses of UVA.32 Several lines of experimental evidence
seem to implicate squalene peroxides as causal agents. Topical application to the ears of rabbits produced lesions similar to those of acne, including hyperkeratosis of the follicular epithelium and proliferation of sebaceous glands to a degree that was correlated with the degree of peroxidation.33,34 In cultured keratinocytes, squalene
hydroperoxides induced cell proliferation and increased the synthesis of the pro-inflammatory cytokine IL-6.35
Kostyuk et al reported that
UV-irradiation of skin surface lipids reduced the concentrations of vitamin E and squalene, while increasing that of oxidised squalene.36 When the irradiated lipids were added to
Figure 2: Stained histological section of a normal pilosebaceous unit
For example, it contains less linoleic acid, whose utilisation for the synthesis of wax esters is a unique property of sebocytes.27 Although the significance of that difference, if any, is not known, a second characteristic of sebum in sufferers seems likely to be important, namely a two-fold greater content of squalene.2 In most cells of the body, squalene is
an intermediate in cholesterol synthesis. However, in sebocytes the next step in cholesterogenesis, the cyclization of squalene to lanosterol, is almost absent. Therefore, although it has not been proven
to be so, it seems likely that the enrichment of sebum with squalene in sufferers reflects a greater rate of synthesis. Certainly, androgens, whose association with acne is clear, induce squalene synthesis in the sebaceous glands.28 Being polyunsaturated, squalene is
susceptible to peroxidation, and irradiation of both squalene in vitro and sebum on skin with UV rapidly converts it to hydroperoxides,29,30 particularly mono-hydroperoxides.31 Mudiyanselage et al have shown that this is a
C
keratinocytes, synthesis of cytokines IL-6 and IL-8 increased. Similar effects were observed when pure squalene that had been irradiated in vitro was added, while non-irradiated squalene and non-irradiated lipids were without effect. Although most research in this field has to
date focused on the biology of sebocytes and keratinocytes, lately increasing attention has been given to the neutrophils and macrophages that infiltrate the pilosebaceous units of early lesions,37
particularly the role of lipids in
reprogramming the cells.38 An elegant series of experiments by Do et al By combining single-
is of particular interest.39
cell RNA sequencing and ultrahigh-resolution analyses of early-stage lesions, they identified macrophages expressing lipid metabolism and pro-inflammatory genes in close proximity to hair follicle epithelial cells expressing an enzyme that oxidises squalene. Tandem experiments in vitro suggested that
products of squalene oxidation were inducing the macrophages to express a lipid-binding receptor called TRAM2. As a consequence, the macrophages accumulated lipids to transform them into foam cells similar to those seen around acne lesions in vivo. Particularly noteworthy was the fact that the macrophages also lost their ability to kill C.
D
Figure 3: A: Growth of C. acnes on blood agar after anaerobic incubation (A. EM Garrett and
PathologyOutlines.com, 2023). B: Stereomicroscopic photograph of C. acnes colonies (Atlas of Oral Biology, Chapter 4, 2015, Pp 67-93) C: Gram-stained C. acnes in thioglycollate medium (US Centres for Disease Control and Prevention, 1972). D: Scanning electron micrograph of C. acnes (Atlas of Oral Biology)
PERSONAL CARE August 2025
www.personalcaremagazine.com
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