Pathogenesis Of Acne Vulgaris Research Articles

The Role of Propionibacterium acnes Biofilm in Acne Vulgaris

Acne vulgaris is traditionally known as the result of excess sebum production, follicular hyper keratinization, infection with Propionibacterium acnes, and follicular inflammation. However, the role of P. acnes is gaining momentum as the primary impetus in the pathogenesis of acne vulgaris. The biofilm-forming ability of P. acnes in vitro and on indwelling medical appliances and catheters has been known for quite some time, but only in the last decade has the presence of P. acnes biofilm been observed within the pilosebaceous unit. Since that time, the genome of the microbe has been sequenced, and genes responsible for quorum sensing and biofilm formation have been confirmed. As a result of biofilm formation, the virulence of P. acnes is amplified. Biofilm-encapsulated P. acnes upregulates the production of lipases, resulting in the production of free fatty acids. Free fatty acids as well as the biofilm itself bind the Toll-like receptors TLR2 and TLR4, activating the innate immune system, culminating in a robust inflammatory response. Biofilms also appear to significantly contribute to antibiotic resistance. Acting as a physical barrier for antibiotics as well as a commune for bacteria to exchange antibiotic resistance genes, the biofilm plays an integral role as the major hurdle to treating acne vulgaris. Traditional antimicrobials have not shown much promise in disruption of the biofilm. Other approaches have been investigated utilizing a variety of novel topical compounds that act to prevent or disrupt the biofilm as a therapeutic modality. The role of biofilm in the pathogenesis of acne vulgaris has remained underappreciated, but with global antimicrobial resistance looming, further attention may be warranted

Immunohistochemical Expression of Cyclo-oxygenase 2 and Liver X Receptor-α in Acne Vulgaris.

Acne Vulgaris (AV) is a common inflammatory disease of pilosebaceous units. Liver X Receptor-α (LXR-α) is a ligand activated transcription factor. It controls transcription of genes involved in lipid and fatty acid synthesis. Cyclo-oxygenase 2 (COX2) is a rate limiting enzyme in prostaglandin synthesis. It plays important role in inflammation. To evaluate the immunohistochemical expression of LXR-α and COX2 in acne vulgaris skin biopsies to explore their possible pathogenic role in this disease. Sixty five subjects were included (45 cases with AV and 20 age and gender-matched healthy controls). Skin biopsies were taken from lesional and perilesional skin of cases and from site-matched areas of control subjects. The evaluation of LXR-α and COX2 was done using immunohistochemical technique. Data were collected, tabulated and statistically analysed using a personal computer with "(SPSS) version 11" program. Chi-square test was used to study the association between qualitative variables. Mann-Whitney test was used for comparison between quantitative variables. Student's t-test was used for comparison between two groups having quantitative variables. Spearman's coefficient was used to study the correlation between two different variables. Differences were considered statistically significant with p<0.05. COX2 was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher epidermal COX2% was significantly associated with papulopustular acne (p=0.009) and higher acne score (p=0.018). Higher pilosebaceous units COX2% was significantly associated with papulopustular acne (p=0.04). LXR-α was upregulated in lesional skin compared with peilesional and control skin both in epidermis and pilosebaceous units (p<0.001 for all). Higher LXR-α % in epidermis and pilosebaceous units was significantly associated with papulopustular acne (p=0.01 for both) and higher acne score (p=0.03 for both). Significant positive correlation was detected between COX2% and LXR-α % in epidermis (p=0.001, r=0.87) and pilosebaceous units (p=0.001, r=0.65). Both LXR-α and COX-2 play a role in the pathogenesis of acne vulgaris through their effects on cellular proliferation, inflammation and lipid synthesis. Research for new therapeutic modalities based on their inhibition is needed. More understanding of the interaction between LXR-α, COX2 and acne lesions may lead to effective interference, possibly directed toward specific cell types or steps within inflammatory pathways.

Editor’s Pick: The Role of Toll-Like Receptors and Antimicrobial Peptides in the Pathogenesis of Acne Vulgaris

Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit. AV has a multifactorial pathogenesis with specific roles played by the sebaceous glands, abnormal follicular hyperkeratinisation, inflammation, Propionibacterium acnes, hormonal factors, immune mediators, and genetic and environmental factors. Significant improvements have been made to elucidate acne pathogenesis, through developments in molecular biology, immunology, and genetic techniques. Toll-like receptors and antimicrobial peptides play significant roles in the host defense system against different pathogenic micro-organisms on the skin and these molecules induce several immunological responses. It is well known that toll-like receptors and antimicrobial peptides play important roles in AV pathogenesis and further understanding of these will contribute to improvements in treatment.

Anti-Acne Activity of Italian Medicinal Plants Used for Skin Infection.

Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: (1) To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI) exhibit significantly more activity against P. acnes than species with no such reported use; and (2) Chemically characterize active extracts and assess their suitability for future investigation. Extracts of Italian medicinal (for acne and other skin infection) and randomly collected plants and fungi were screened for growth-inhibitory and anti-biofilm activity in P. acnes using broth microdilution methods. Bioactive extracts were chemically characterized by HPLC and examined for cytotoxicity against human keratinocytes (HaCaTs). Following evaluation of 157 extracts from 10 fungi and 58 plants, we identified crude extracts from seven species exhibiting growth inhibitory activity (MICs 64–256 μg mL−1). All active extracts were examined for cytotoxicity against HaCaTs; extracts from one fungal and one plant species were toxic (IC50 256 μg mL−1). HPLC analysis with chemical standards revealed many of these extracts contained chlorogenic acid, p-coumaric acid, ellagic acid, gallic acid, and tannic acid. In conclusion, species used in traditional medicine for the skin exhibited significantly greater (p < 0.05) growth inhibitory and biofilm eradication activity than random species, supporting the validity of an ethnobotanical approach to identifying new therapeutics. The anti-acne activity of three extracts is reported for the first time: Vitis vinifera leaves, Asphodelus microcarpus leaves, and Vicia sativa aerial parts.

A comparative study of MMP-1, MMP-2, and TNF-α expression in different acne vulgaris lesions.

Many inflammatory mediators and cytokines play important roles in the pathogenesis of acne vulgaris (AV). Information about the roles of these factors in the pathogenesis of the disease is limited. The purpose of this study was to evaluate levels of matrix metalloproteinase-1 (MMP-1), MMP-2, and tumor necrosis factor-α (TNF-α) in AV lesions. We selected 80 patients who presented at our dermatology department with AV. Their lesions included papules, pustules, nodules, and comedones. Each specimen was evaluated by histopathology with hematoxylin and eosin staining, and subsequently by immunohistochemical analysis for MMP-1, MMP-2, and TNF-α antibodies. A statistically significant difference between lesion groups emerged for MMP-1 (P = 0.012) and TNF-α (P = 0.029) scores. The MMP-1 score was highest in nodules and lowest in comedones. The TNF-α score was also highest in nodules but lowest in papules. We conclude that different levels of MMP expression can contribute to the development of different types of acne lesion and that the amount of TNF-α released may contribute to lesion development. Further studies of novel treatment modalities might evaluate the different clinical types of AV.

Evaluation of leptin, adiponectin, and ghrelin levels in patients with acne vulgaris.

The research evaluating adipokines are very few in patients with acne vulgaris. The hypothesis that hyperinsulinemic and high glycemic index diet plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as leptin (L), adiponectin (A), ghrelin and A levels, and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris. Thirty patients who are nonobese with moderate acne vulgaris, aged 18 to 25 years, and 15 age-sex compatible controls were included in our study. The acne lesions were assessed using the Global Acne Grading Scale (GAGS). All participants were evaluated for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood, and their body mass index were calculated. The significance level was determined as p ≤ 0.05. Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease were 2.8 years. All of patients had moderate acne vulgaris (GAGS 19-30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the two groups. Adipokines may have a role in the pathogenesis of acne vulgaris. L, A, ghrelin, and insulin resistance may not participate in the responsible mechanisms in nonobese patients with moderate acne vulgaris.

Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris

There is increasing evidence to support the relationship between acne vulgaris and diet. The aim of this study was to investigate possible associations among dietary glycemic index, glycemic load, milk consumption, insulin resistance, and adiponectin levels in the pathogenesis of acne vulgaris. The dietary glycemic index, glycemic load, milk consumption, fasting glucose, insulin, insulin-like growth factor)-1, insulin-like growth factor binding protein-3, adiponectin, and homeostasis model assessment of insulin resistance values of 50 patients with acne vulgaris and 36 healthy control subjects were measured. Glycemic index and glycemic load levels were significantly higher (P=.022 and P=.001, respectively) and serum adiponectin levels were significantly lower (P=.015) in patients with acne than in the control subjects. There was an inverse correlation between serum adiponectin concentration and glycemic index (P=.049, r=-0.212). This study used a cross-sectional design and the study population was limited to young, nonobese adults. A high-glycemic-index/-load diet was positively associated with acne vulgaris. Adiponectin may be a pathogenetic cofactor contributing to the development of the disease. Furtherresearch on adiponectin levels in patients with acne in terms of development of insulin resistance might be important in this possible relationship.

Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G>A and -420C>G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment.

Survivin as a Novel Biomarker in the Pathogenesis of Acne Vulgaris and Its Correlation to Insulin-Like Growth Factor-I.

Survivin, a member of the inhibitor of apoptosis protein family, has an important role in cell cycle regulation. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone with wide range of biologic effects including stimulation of lipogenesis in sebaceous glands. Their overexpression in some fibrotic disorders suggests a possible implication of both IGF-I and survivin in the pathogenesis of acne and/or acne scars. The current study aimed to assess and correlate serum levels of IGF-I and survivin in patients with active acne vulgaris and postinflammatory acne scars and to evaluate their lesional expressions in comparison to healthy controls. Serum IGF-I and survivin were estimated using commercially available ELISA kits and their tissues expressions were investigated using Western blotting. Our findings suggest that IGF-I and survivin could play potential roles in the pathogenesis of active acne vulgaris and more importantly in postinflammatory acne scars with significant positive correlation coefficient between serum levels of IGF-I and survivin which support IGF-I-/PI3K-/AKT-mediated downregulation of nuclear expression of FoxO transcription factors resulting in enhanced survivin expression.

Significance of diet in treated and untreated acne vulgaris.

The relationship between diet and acne is highly controversial. Several studies during the last decade have led dermatologists to reflect on a potential link between diet and acne. This article presents the latest findings on a potential impact that diet can have on pathogenesis of acne vulgaris. The association between diet and acne can no longer be dismissed. Compelling evidence shows that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne and the roles of omega-3 fatty acids, dietary fiber, antioxidants, vitamin A, zinc and iodine remain to be elucidated. The question of what the impact of diet is on the course of acne vulgaris still remains unclear.

Comparison of TLR-2, TLR-4, and antimicrobial peptide levels in different lesions of acne vulgaris

Context: Recent studies have shown that tolls like receptors (TLRs) and antimicrobial peptides (hBD-1, cathelicidin) play an important role in the pathogenesis of acne vulgaris (AV).Objective: To evaluate and report the expression of TLR-2, TLR-4, hBD-1 and cathelicidin in different regions of skin in AV.Participants: This study was performed in 80 patients with AV and a control group of 20 healthy individuals.Material and methods: Skin biopsies were performed from 20 papular, 20 pustular, 20 comedonal and 20 nodular lesions of patients and 20 healthy volunteers. Expression levels of TLR-2, TLR-4, hBD-1 and cathelicidin in four separate areas (epidermis, dermis, inflammation region and skin appendages) were evaluated by immunohistochemical method. Further, these parameters were compared between different skin lesions.Results: A significant difference was found between the levels of staining of TLR-2, TLR-4 and hBD-1 from the epidermis, inflammation region, dermis and skin appendages (p < 0.05). Levels of cathelicidin were different in only the inflammation region (p < 0.05). The level of TLR-2 in the epidermis with nodules was lower than the papules and comedones (p < 0.05). Levels of TLR-2 in the inflammation and dermis of the cases with papules were significantly higher when compared to pustules (p < 0.05). The levels of staining of TLR-4 in the dermis with comedones were significantly lower compared to the cases with papules (p < 005). The level of hBD-1 in the epidermis region of comedones was significantly higher compared to nodules (p < 0.05). The expression of cathelicidin in the inflammation region of comedones was significantly low (p < 0.05).Conclusion: It is thought that TLR-2, TLR-4, hBD-1 and cathelicidin play an important role in the pathogenesis of AV and in the development of different acne types. We think that, better results could be obtained in treatment of AV with different treatment options targeted in regulation of TLR-2, TLR-4, hBD-1 and cathelicidin release.

Salty and spicy food; are they involved in the pathogenesis of acne vulgaris? A case controlled study

Many studies have suggested a strong relation between diet and acne. Many patients with acne believe that spicy and salty foods exacerbate acne. To assess the relationship between the dietary intake of salty and spicy food and the onset, severity, duration of acne. Two hundred patients with acne vulgaris and 200 age- and gender-matched controls were subjected to a detailed questionnaire taking, clinical examination and dietary assessment through using "24h recall" method. Sodium content of the 24-h food intake was computed by a computer program connecting participants' dietary information to the food composition table of National Nutrition Institute data base. Patients with acne consumed significantly higher daily amounts of sodium chloride (NaCl) (median 3367.54mg) compared to the controls (median 2271.8mg) (P<0.001). A negative correlation between the amount of NaCl in the diet of patients with acne and the age of onset of acne lesions was detected (r=-0.216, P=0.031). However, neither salty nor spicy food correlated with duration or severity of the disease. Consumption of salty foods was significantly higher among patients with acne compared to acne free subjects, making the consumption of salty food a possible participating factor in the development of acne.

Ghrelin in the pilosebaceous unit: alteration of ghrelin in patients with acne vulgaris.

Ghrelin in the pilosebaceous tissues of human skin and ghrelin levels in patients with acne vulgaris have not yet been investigated. The purpose of this study was to screen ghrelin immunoreactivity by immunohistochemistry in human pilosebaceous tissues of human skin and also to determine the quantities of ghrelin in the serum of the patients with acne vulgaris. 30 patients presenting with acne vulgaris and 30 control subjects participated in this study. Ghrelin levels were determined by enzyme linked immunosorbent assay (ELISA). Human hair follicles and sebaceous glands were immunohistochemically examined. Immunohistochemistry results showed that there is a strong ghrelin immunoreactivity in the hair follicles and sebaceous glands in sections of human skin. The mean serum ghrelin levels (27.58 ・} 15.44 pg/mL) in patients with acne vulgaris was significantly lower than those of controls (35.62・}20.46 pg/mL). Ghrelin produced in hair follicles and sebaceous glands of the skin might participate in the pathogenesis of acne vulgaris and also acne vulgaris in humans might be associated with decreased serum ghrelin.

The RETN gene rs1862513 polymorphism as a novel predisposing marker for familial Acne vulgaris in a Pakistani population.

Resistin (RETN), recently found to be relevant to inflammation and inflammatory disorders. We, therefore, aimed to investigate the potential role of RETN gene polymorphism in pathogenesis of acne vulgaris with familial history. We investigated the RETN-420C/G polymorphism in 180 patients with acne vulgaris and 180 healthy individuals in a case-control association analysis. In this study, we also investigated the heritability of the RETN susceptible allele from 140 trio families with acne affected offspring. The genotyping was performed by polymerase chain reaction and direct DNA sequencing. The RETN-420C/G polymorphism was significantly associated with acne in patients compared with healthy controls (P=0.014). The minor allele G at -420 was more prevalent in cases vs. controls (P=0.002). The RETN-420C/G polymorphism was significantly associated with severity of acne vulgaris in patients (P=0.0097). The results of a transmission disequilibrium test revealed a significant association between the RETN-420C/G polymorphism and acne vulgaris (P<0.001). For the first time in the literature, to our knowledge, we demonstrate a significant association of the RETN-420C/G functional polymorphism with familial acne vulgaris.

Propionibacterium acnes Promotes Th17 and Th17/Th1 Responses in Acne Patients

Propionibacterium acnes is a Gram-positive commensal bacterium thought to be involved in the pathogenesis of acne vulgaris. Although the ability of P. acnes in the initiation of pro-inflammatory responses is well documented, little is known about adaptive immune responses to this bacterium. The observation that infiltrating immune cells consist mainly of CD4(+) T cells in the perifollicular space of early acne lesions suggests that helper T cells may be involved in immune responses caused by the intra-follicular colonization of P. acnes. A recent report showing that P. acnes can induce IL-17 production by T cells suggests that acne might be a T helper type 17 (Th17)-mediated disease. In line with this, we show in this work that, in addition to IL-17A, both Th1 and Th17 effector cytokines, transcription factors, and chemokine receptors are strongly upregulated in acne lesions. Furthermore, we found that, in addition to Th17, P. acnes can promote mixed Th17/Th1 responses by inducing the concomitant secretion of IL-17A and IFN-γ from specific CD4(+) T cells in vitro. Finally, we show that both P. acnes-specific Th17 and Th17/Th1 cells can be found in the peripheral blood of patients suffering from acne and, at lower frequencies, in healthy individuals. We therefore identified P. acnes-responding Th17/Th1 cells as, to our knowledge, a previously unreported CD4(+) subpopulation involved in inflammatory acne.

Longitudinal, 3D In Vivo Imaging of Sebaceous Glands by Coherent Anti-Stokes Raman Scattering Microscopy: Normal Function and Response to Cryotherapy

Sebaceous glands perform complex functions, and are centrally involved in the pathogenesis of acne vulgaris. Current techniques for studying sebaceous glands are mostly static in nature, whereas the gland’s main function – excretion of sebum via the holocrine mechanism – can only be evaluated over time. We present a longitudinal, real-time alternative – the in vivo, label-free imaging of sebaceous glands using Coherent Anti-Stokes Raman Scattering (CARS) microscopy, which is used to selectively visualize lipids. In mouse ears, CARS microscopy revealed dynamic changes in sebaceous glands during the holocrine secretion process, as well as in response to damage to the glands caused by cooling. Detailed gland structure, plus the active migration of individual sebocytes and cohorts of sebocytes were measured. Cooling produced characteristic changes in sebocyte structure and migration. This study demonstrates that CARS microscopy is a promising tool for studying the sebaceous gland and its associated disorders in three-dimensions in vivo.

The interleukin-6 and interleukin-1A gene promoter polymorphism is associated with the pathogenesis of acne vulgaris.

Acne vulgaris is a skin disorder with a complex pathogenesis. Better treatment strategies require comprehensive knowledge of molecular factors contributing to the acne pathophysiology. Recent studies are focused on investigating the influence of inflammatory cytokines on the disease. This case-control study investigated the association of IL-6-572 G/C and IL-1A-889 C/T gene polymorphisms with acne in a Pakistani population. Pakistani subjects (380 healthy controls and 430 acne patients) were enrolled in this study. Polymorphism in the promoter region of IL-6-572 and IL-1A-889 was determined by polymerase chain reaction and restriction fragment length polymorphism. The IL-6-572 and IL-1A-889 variant genotypes were significantly associated with the acne pathogenesis. The IL-6-572C and the IL-1A-889T alleles were significantly high in the patient vs. control group (p < 0.0001 for both loci). The IL-6-572 G/C and IL-1A-889 C/T variant allele haplotypes showed significantly high prevalence in patients with acne; G-T (P = 0.0014), C-C (P < 0.0001), and C-T (P < 0.0001). This is the first report on the association between the IL-6-572 G/C polymorphism and acne among any population. The IL-1A-889 C/T polymorphism is also significantly linked with acne in the study population; the -889 C/T association with acne has been reported in one ethnic group previously. Our findings suggest that the IL-6-572C and IL-1A-889T alleles may contribute to the pathogenesis of acne in a Pakistani population. Further studies are required to verify these findings in other populations.

Role of hormones and blood lipids in the pathogenesis of acne vulgaris in non-obese, non-hirsute females.

Context:Acne vulgaris (AV) is a common disease affecting all ages and ethnic groups. Androgens, skin and serum lipids, inflammatory signaling and regulatory neuropeptides seem to be involved in this multi-factorial process.Aim:The aim of this work was to determine hormonal levels and lipid profile in non-obese, non-hirsute females with AV.Subjects and Methods:A total of 60 non-obese, non-hirsute female cases with different grades of AV and 60 age- and gender-matched healthy volunteers were included. Measurement of serum total and free testosterone, sex hormone binding globulin (SHBG), estradiol and progesterone and blood lipids was done during the luteal phase of the menstrual cycle.Results:Total testosterone, free testosterone (FT) and progesterone levels were significantly higher (P < 0.001 for all) while estradiol levels (P < 0.001) and SHBG (P < 0.01) were significantly lower in cases than controls. Total cholesterol and low density lipoprotein cholesterol (LDL-C) levels were significantly higher (P < 0.001 for both) while high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1) levels were significantly lower (P < 0.001 for both) in cases than controls. Higher values of FT (P = 0.03) and SHBG (P = 0.02) and lower values of estradiol (P = 0.04) levels were significantly in favor of severe acne. Higher values of cholesterol (P < 0.001) and LDL-C (P = 0.03) and lower values of HDL-C (P = 0.01) and ApoA-1 (P = 0.02) levels were significantly associated with severe acne.Conclusion:Changes in hormone levels and lipid profile in non-obese and non-hirsute females with AV should be considered in disease pathogenesis and in treatment prescription of these patients.

Correlation between the severity and type of acne lesions with serum zinc levels in patients with acne vulgaris.

Acne vulgaris is the most common cutaneous disorder affecting adolescents and young adults. Some studies have reported an association between serum zinc levels and acne vulgaris. We aimed to evaluate the serum zinc level in patients with acne vulgaris and compare it with healthy controls. One hundred patients with acne vulgaris and 100 healthy controls were referred to our clinic. Acne severity was classified according to Global Acne Grading System (GAGS). Atomic absorption spectrophotometry was used to measure serum zinc levels. Mean serum level of zinc in acne patients and controls was 81.31 ± 17.63 μg/dl and 82.63 ± 17.49 μg/dl, respectively. Although the mean serum zinc level was lower in acne group, it was not statistically significant (P = 0.598). There was a correlation between serum zinc levels with severity and type of acne lesions. The results of our study suggest that zinc levels may be related to the severity and type of acne lesions in patients with acne vulgaris. Relative decrease of serum zinc level in acne patients suggests a role for zinc in the pathogenesis of acne vulgaris.

Investigating how bacteriophages influence the human immune response to Propionibacterium acnes (P3148)

Abstract Numerous lines of evidence implicate the Gram-positive skin commensal, Propionibacterium acnes, in the pathogenesis of acne vulgaris, in part by eliciting a host inflammatory response. The emergence of antibiotic resistance in up to 60% of P. acnes isolates, along with the adverse side effects of current treatments has highlighted the need for the development of safer and more effective anti-acne therapeutics. We have investigated the bacteriophages that infect and kill P. acnes and found that they have limited genetic diversity and broad host ranges against clinical isolates, pointing to the potential utility of a phage-based acne treatment. Here, we explored whether these phages, by lysing P. acnes, influence the human immune response to the bacteria. Human monocytes were cultured in the presence of phage-killed or live bacteria, and cytokine responses were measured. We found that monocytes cultured with phage-killed bacteria secrete lower levels of pro-inflammatory cytokines, such as TNFα, IL-1β and IL-12p40, as compared to those infected with live bacteria; phage alone did not stimulate a response. This pattern was also observed when phage and bacteria were added concurrently, that is, during active phage infection, and in all cases, this was consistent across multiple donors. These data suggest that bacteriophage-mediated killing of P. acnes bacteria could help to ameliorate the inflammation associated with acne as a therapeutic modality.