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David E Castillo,1 Jonette E Keri1,2 1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; 2Dermatology Service, Miami VA Hospital, Miami, FL, USA Abstract: Acne vulgaris is the most common skin disorder in adolescents and young adults. It carries a significant psychological and economic burden to patients and society. A wide range of therapeutic options are available, including topicals and systemic therapies. Chemical peeling is a skin resurfacing procedure intended to regenerate normal skin from the application of exfoliative agents. It has been used for the treatment of acne vulgaris and other skin disorders for decades. There are several chemical agents with variable mechanisms of action, usually classified as superficial, medium, and deep peels. When selecting the patient and the appropriate peel, the dermatologist individualizes therapy, and performs an extensive interview, including past medical history and physical exam. Several host factors can affect the outcome of this procedure, including current psychological state, medications, history of surgery, and immune system, among others. The physician must also be confident that the peel is safe and effective for the target patient. The Fitzpatrick skin type scale is a useful tool to classify patients based on skin color and ability to tan, but also can be used to evaluate preoperative risk of postpeel response and complications. Dark-skinned patients (Fitzpatrick skin type IV–VI), including blacks, Asian, and Hispanic/Latino, are at higher risk of postinflammatory/postpeel hyperpigmentation. When treating these populations, deep chemical peels should be avoided, and preoperative preparation emphasized. There are many studies available in the literature supporting the use of superficial to medium depth peels as adjuvant therapy for acne vulgaris. This review article aims to present the most important factors when selecting a patient for a chemical peel, the evidence behind its safety and efficacy, and special considerations when choosing a specific agent. Keywords: chemical peels, acne, patient perspective, specific population, peel complications

Background: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older., Objective: The objective of this study was to provide evidence-based recommendations for the management of acne., Methods: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations., Results: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements., Limitations: Analysis is based on the best available evidence at the time of the systematic review., Conclusions: These guidelines provide evidence-based recommendations for the management of acne vulgaris., Competing Interests: Conflicts of interest Rachel V.S. Reynolds, MD, Carol E. Cheng, MD, Kelly Druby, Megha M. Tollefson, MD, and Jung Min Han, PharmD, MS, have no relationships to disclose. Howa Yeung, MD, MS, serves as an investigator for American Acne & Rosacea Society, Department of Veterans Affairs, and National Institutes of Health receiving grants and research funding; as an independent contractor for American Academy of Dermatology and Journal of the American Medical Association receiving fees; as a speaker/faculty educator for Dermatology Digest receiving honoraria. Fran Cook-Bolden, MD, serves as an advisory board member for AbbVie, Dermavant Sciences, Inc., Galderma Global, Novartis, Ortho Dermatologics, and Pfizer Inc. receiving honoraria; as an investigator for Arcutis Biotherapeutics receiving grant and research funding; as a speaker for Galderma Laboratories, LP, Journey Medical Corporation, and Ortho Dermatologics receiving honoraria; as others for Topix Pharmaceuticals, Inc. receiving other financial benefit. Seemal R. Desai, MD, serves an advisory board member for Foundation for Research & Education of Dermatology receiving fees; as a consultant for AbbVie, Allergan, Inc, Almirall, Amgen, Apogee, Avita, Ballature Beauty, Beiersdorf, Inc., Bristol-Myers Squibb, Candela Corporation, Cassiopea S.p.A., Castle Biosciences, Cutera, Inc., Dermavant Sciences, Dermira, Eli Lilly and Company, EPI Health, Ferndale Laboratories, Inc., Foamix, Galderma Laboratories, LP, Gore Range Capital, Hyphens Pharma, Incyte Corporation, Janssen Pharmaceuticals, Inc, Johnson and Johnson, Leo Pharma Inc., L'Oreal USA Inc., Lyceum Health, Ortho Dermatologics, Pfizer Inc., Revision Skincare, Sanofi/Regeneron, Scientis, Skin Science Advisors, UCB, Verrica Pharmaceuticals Inc., and VYNE Therapeutics receiving fees, honoraria, and/or stock options; as an investigator for AOBiome, LLC, Atacama Therapeutics, Dermavant Sciences, Incyte Corporation, and SkinMedica, Inc. receiving grants and research funding; as a speaker for AbbVie, Dermira, Galderma Laboratories, LP., and Pfizer Inc. receiving fees; as a stockholder for Gore Range Capital; as other role for Medscape receiving fees. Esther E. Freeman, MD, PhD, serves as an investigator for International League of Dermatologic Societies and National Institutes of Health receiving grants and research funding; as an author for UptoDate, Inc. and British Journal of Dermatology, receiving honoraria or salary; as a speaker for Harvard University. Jonette E. Keri, MD, PhD, serves as an advisory board member for Ortho Dermatologics receiving honoraria; as a consultant for Almirall receiving fees; as an investigator for Galderma USA receiving grants and research funding; as a speaker for Foamix Pharmaceuticals Ltd and VYNE Therapeutics receiving honoraria. Linda F. Stein Gold, MD, serves as an advisory board member for AbbVie, Almirall, Aqua, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., GlaxoSmithKline, Incyte Corporation, La Roche-Posay Laboratorie Pharmaceutique, LEO Pharma, US, Lilly ICOS LLC, Merz Pharmaceuticals, LLC, Pfizer Inc., Promius Pharmaceuticals, Sanofi/Regeneron, Taro Pharm, and Valeant Pharmaceuticals International receiving honoraria; as a consultant for AnaptysBio, BMS, Botanix Pharmaceuticals, Cutera, Inc., Incyte Corporation, Janssen Scientific Affairs, LLC, Sol-Gel Technologies, Taro Pharm, The Acne Store, and UCB receiving honoraria or grants and research funding; as an investigator for AbbVie, Allergan, Inc., AnaptysBio, Galderma Laboratories, L.P., Leo Pharma Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Topica, and Valeant Pharmaceuticals International receiving grants and research funding; as a speaker for Actavis, Almirall, BMS, Dermira, Pfizer Inc., Sanofi/Regeneron, Sun Pharmaceutical Industries Ltd., and VYNE Therapeutics receiving honoraria. Jerry K. L. Tan, MD, serves as an advisory board member for Abbott Laboratories, Cutera, Inc., Galderma Laboratories, L.P, and Sun Pharmaceutical Industries Ltd receiving honoraria or grants and research funding; as a consultant for Bausch Health, Boots, Galderma Research & Development, LLC, and Loreal Research and Innovation receiving honoraria; as an independent contractor for Norvatis receiving fees; as an investigator for Allergan, AnaptysBio, Cutera, Inc., Eli Lilly and Co., Galderma Laboratories, L.P, Lilly ICOS LLC, Pfizer, and UCB for receiving grants and research funding; as a speaker for Bausch Health, LEO Laboratories Ltd (LEO Pharma), and Vichy Laboratories receiving honoraria. Jonathan S. Weiss, MD, serves as an advisory board member for Bristol-Myers Squibb, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., Incyte Corporation, Novartis, and UCB receiving honoraria; as a consultant for Arcutis, Inc., Biofrontera, Cutera, Inc., Leo Pharma Inc, Ortho Dermatologics, and UCB receiving fees or honoraria; as an investigator for AbbVie, Bausch Health, Biofrontera, Bristol-Myers Squibb, Cutera, Inc., Dermavant Sciences, Foamix, Galderma Laboratories, L.P., LEO Pharma, Mindera, Moberg Pharma North, America LLC, Novartis, Palvella Therapeutics, and Verrica Pharmaceuticals Inc receiving grants and research funding; as a speaker for AbbVie, Arcutis, Inc., Galderma Laboratories, L.P., Ortho Dermatologics, Regeneron, and Sanofi Genzyme receiving honoraria. Peggy A. Wu, MD, serves as others for UptoDate, Inc. receiving honoraria. Andrea L. Zaenglein, MD, serves as a consultant for Church & Dwight Co., Inc. and UCB receiving fees or honoraria; as an investigator for AbbVie, Arcutis Biotherapeutics, Biofrontera AG, Galderma Laboratories, L.P., and Incyte Corporation receiving grants and research funding. John S. Barbieri, MD, MBA serves as investigator for National Institutes of Health and National Psoriasis Foundation receiving grants and research funding., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The growing demand for natural treatments has raised concerns among clinicians due to limited scientific evidence supporting their use. This review article addresses the issue by assisting dermatologists and general practitioners in recommending natural treatments for the following common nail disorders: nail brittleness, onychomycosis, periungual verrucae, paronychia, chloronychia, nail psoriasis, nail lichen planus, onychocryptosis, onycholysis, and congenital malalignment of the great toenail. One limitation is the scarcity of existing reviews on natural treatment options for nail disorders in the literature. Through a comprehensive review of existing literature, this article consolidates the available evidence on natural treatment options for these conditions. Although some natural treatments for nail disorders are supported by scientific evidence, the indiscriminate use of such remedies may lead to severe poisoning and health problems. Given the widespread and increasing use of natural treatments, clinicians play a pivotal role in educating patients about evidence-based remedies and debunking misleading claims. By doing so, clinicians can enhance patient safety and improve treatment outcomes. It is essential for healthcare professionals to be well-informed and equipped with the knowledge to differentiate between effective natural treatments and unverified claims, ensuring that patients receive appropriate care., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Acne is a chronic inflammatory disease of the pilosebaceous unit with a multifactorial etiology and is one of the most common conditions treated by dermatologists and primary care physicians. Within an extensive and evolving treatment landscape, oral isotretinoin has demonstrated efficacy for treatment of severe, recalcitrant acne. Several side effects of isotretinoin have been reported, including laboratory abnormalities, mucocutaneous, and musculoskeletal effects, which may reduce compliance and patient satisfaction with treatment. In this narrative review, we aim to review the efficacy and safety profile of oral supplements or topical adjuvant therapies in mitigating isotretinoin-associated mucocutaneous and musculoskeletal side effects. Oral supplements reviewed include omega-3 fatty acids, vitamin E, folic acid and vitamin B12, antihistamines, l-carnitine, biotin, and combined oral supplements. Topical adjuvants include a hyaluronic acid, biosaccharide gum-2, and glycerine gel-cream; a nongreasy, noncomedogenic, fragrance-free moisturizing cream; dexpanthenol; trichloroacetic acid; and a combination cream. Most of the supplements and topical adjuvants demonstrated efficacy with an adequate level of supporting evidence and no reported adverse events, indicating an adequate safety profile. Patients on isotretinoin may benefit from using oral supplements and topical adjuvants to minimize primarily mucocutaneous side effects, increase adherence to treatment, and thereby improve overall outcomes., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Acne vulgaris is a common condition that routinely affects females of childbearing age. Taking into consideration the reproductive journey of women when treating acne is of paramount importance given the safety concerns to both the mother and the fetus associated with certain medications. Therefore, careful consideration of therapeutic choices during pregnancy is crucial. Herein, we summarize the safety of acne treatments during pregnancy and offer practical clinical pearls for routine dermatology practice.

Obesity is a worldwide major public health problem with an alarmingly increasing prevalence over the past 2 decades. The consequences of obesity in the skin are underestimated. In this paper, we review the effect of obesity on the skin, including how increased body mass index affects skin physiology, skin barrier, collagen structure, and wound healing. Obesity also affects sebaceous and sweat glands and causes circulatory and lymphatic changes. Common skin manifestations related to obesity include acanthosis nigricans, acrochordons, keratosis pilaris, striae distensae, cellulite, and plantar hyperkeratosis. Obesity has metabolic effects, such as causing hyperandrogenism and gout, which in turn are associated with cutaneous manifestations. Furthermore, obesity is associated with an increased incidence of bacterial and Candida skin infections, as well as onychomycosis, inflammatory skin diseases, and chronic dermatoses like hidradenitis suppurativa, psoriasis, and rosacea. The association between atopic dermatitis and obesity and the increased risk of skin cancer among obese patients is debatable. Obesity is also related to rare skin conditions and to premature hair graying. As physicians, understanding these clinical signs and the underlying systemic disorders will facilitate earlier diagnoses for better treatment and avoidance of sequelae., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Acne vulgaris is the most common dermatological disorder worldwide. It is a multifactorial disease that involves increased sebum production, hyperkeratinization of the pilosebaceous unit, Propionibacterium acnes (Cutibacterium acnes) colonization, and inflammation. The human skin microbiome hosts a wide variety of microorganisms, including bacteria, viruses, and fungi. A delicate balance of these microorganisms is essential for the barrier function of the skin. Propionibacterium acnes represents nearly 90% of the human skin microbiome of healthy adults. Acne is a chronic recurrent disease that requires long-lasting treatment, which has led to the emergence of antibiotic resistance. New alternatives to traditional therapy are emerging, including antimicrobial peptides, natural engineered antibodies, and bacteriophages. Bacteriophages have been shown to play a role in human skin health and disease. There is evidence supporting phage therapy in many types of skin infections. P. acnes bacteriophages have been isolated and characterized. However, only a few in vitro studies have tested the ability of bacteriophages to kill P. acnes. Furthermore, there is no evidence on bacteriophage therapy in the treatment of acne in humans. In this review, we summarize the most recent evidence regarding P. acnes bacteriophages and the potential role of these bacteriophages in the treatment of acne. Further research on this field will provide the evidence to use phage therapy to decrease rates of antibiotic resistance and restore antibiotic susceptibility of P. acnes.

Seborrheic dermatitis (SD) is a chronic, recurring inflammatory skin disorder that manifests as erythematous macules or plaques with varying levels of scaling associated with pruritus. The condition typically occurs as an inflammatory response to Malassezia species and tends to occur on seborrheic areas, such as the scalp, face, chest, back, axilla, and groin areas. SD treatment focuses on clearing signs of the disease; ameliorating associated symptoms, such as pruritus; and maintaining remission with long-term therapy. Since the primary underlying pathogenic mechanisms comprise Malassezia proliferation and inflammation, the most commonly used treatment is topical antifungal and anti-inflammatory agents. Other broadly used therapies include lithium gluconate/succinate, coal tar, salicylic acid, selenium sulfide, sodium sulfacetamide, glycerin, benzoyl peroxide, aloe vera, mud treatment, phototherapy, among others. Alternative therapies have also been reported, such as tea tree oil, Quassia amara, and Solanum chrysotrichum. Systemic therapy is reserved only for widespread lesions or in cases that are refractory to topical treatment. Thus, in this comprehensive review, we summarize the current knowledge on SD treatment and attempt to provide appropriate directions for future cases that dermatologists may face.

Usage of photopneumatic technology has recently increased for treatment of different skin conditions such as acne, keratosis pilaris (KP), and rosacea. Photopneumatic devices combine gentle negative pressure with broad band pulsed light simultaneously to attack multiple targets in the skin for better treatment outcomes. In this literature review, we evaluate the efficacy of photopneumatic therapy on treatment of acne, keratosis pilaris (KP), and rosacea.

Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States., Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma., Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years., Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization., Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers., Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed., Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma., Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

Acne vulgaris is a chronic disease of the pilosebaceous units presenting as inflammatory or noninflammatory lesions in individuals of all ages. The current standard of treatment includes topical formulations in the forms of washes, gels, lotions, and creams such as antibiotics, antibacterial agents, retinoids, and comedolytics. Additionally, systemic treatments are available for more severe or resistant forms of acne. Nevertheless, these treatments have shown to induce a wide array of adverse effects, including dryness, peeling, erythema, and even fetal defects and embolic events. Zinc is a promising alternative to other acne treatments owing to its low cost, efficacy, and lack of systemic side effects. In this literature review, we evaluate the effectiveness and side-effect profiles of various formulations of zinc used to treat acne., (© 2017 Wiley Periodicals, Inc.)

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti-inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient's baseline or performed similarly to another standard-of-care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first-line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time., (© 2017 Wiley Periodicals, Inc.)

Acne keloidalis nuchae (AKN) is a chronic inflammatory condition that leads to fibrotic plaques, papules and alopecia on the occiput and/or nape of the neck. Traditional medical management focuses on prevention, utilization of oral and topical antibiotics, and intralesional steroids in order to decrease inflammation and secondary infections. Unfortunately, therapy may require months of treatment to achieve incomplete results and recurrences are common. Surgical approach to treatment of lesions is invasive, may require general anesthesia and requires more time to recover. Light and laser therapies offer an alternative treatment for AKN. The present study systematically reviews the currently available literature on the treatment of AKN. While all modalities are discussed, light and laser therapy is emphasized due to its relatively unknown role in clinical management of AKN. The most studied modalities in the literature were the 1064-nm neodymium-doped yttrium aluminum garnet laser, 810-nm diode laser, and CO2 laser, which allow for 82-95% improvement in 1-5 sessions. Moreover, side effects were minimal with transient erythema and mild burning being the most common. Overall, further larger-scale randomized head to head control trials are needed to determine optimal treatments.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The rapid increase in the medical use of probiotics and prebiotics in recent years has confirmed their excellent safety profile. As immune modulators, they have been used in inflammatory skin conditions, such as atopic dermatitis. We review the literature regarding the use of probiotics and prebiotics in dermatology. Probiotics and prebiotics appear to be effective in reducing the incidence of atopic dermatitis in infants, but their role in atopic dermatitis treatment is controversial. Their role in acne, wound healing, and photoprotection is promising, but larger trials are needed before a final recommendation can be made., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

We report the first documented case of an atypical form of transient reactive papulotranslucent acrokeratoderma (TRPA) in a patient heterozygous for the ΔF508 CFTR(cystic fibrosis transmembrane conductance regulator) mutation. TRPA represents a condition that classically presents with translucent to white plaques that become evident after water exposure. An atypical form with persistent lesions has also been described. Our patient is a 16-year-old girl with small, white papules coalescing into pebbly plaques on the palms. This condition is exacerbated after 5-10 min of water exposure and is associated with discomfort. The skin biopsy showed expanded stratum corneum, orthohyperkeratosis and dilation of eccrine ducts consisting with TRPA. A cystic fibrosis carrier state, barrier function defect, hyperhidrosis and the intake of cyclooxygenase inhibitors may have been pathogenic factors in our patient., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Diet plays an important role in the pathogenesis of a variety of diseases. Recently, there has been an increasing interest in the role of diet in the development of common skin conditions such as acne and rosacea. The association of diet and acne has been controversial and unclear. Historically, it was thought that diet did not cause acne; however, recent studies reveal a potential role of diet in the pathogenesis of acne. Individuals that have a diet with a high glycemic load or increased milk consumption are reported to have a greater likelihood of having acne. This effect may be mediated by insulin-like growth factor-1 (IGF-1) since IGF-1 levels increase with milk consumption and with a high glycemic load and are known to contribute to the formation of acne. In contrast to acne, the association of diet and rosacea is much more accepted and established. There are a variety of foods that aggravate rosacea, including spicy foods, alcoholic beverages, and hot, caffeinated drinks. Patients are advised to avoid these triggers. Interestingly, omega-3 and omega-6 fatty acids may be beneficial in the treatment of rosacea, although further investigation is necessary. Understanding the etiologic role of diet in acne and rosacea may help in the prevention and treatment of these conditions.

Many safe and effective treatments are available to the acne sufferer. The clinician is encouraged to offer treatment to the adolescent with a face full of pimples, even if not asked for by the patient, as psychosocial underpinnings may be present but not obvious on examination. Obvious physical benefits will result, but psychosocial improvements also may occur.

A case of purpura fulminans in a 44 year old woman infected with malaria is reported. The patient had laboratory findings consistent with disseminated intravascular coagulation and a severe eruption consisting of hemorrhagic bullae and crusts. This case is presented to elucidate another cutaneous manifestation of malaria.

The production of collagen-degrading proteases by cultured neonatal rat microglia was examined using an immobilized fibronectin-gelatin matrix coupled to a fluorescent marker and by substrate gel analysis. When microglia were plated onto the surface of the matrix and incubated under resting (nonstimulated) conditions, a small but visible amount of immobilized matrix was degraded. Treatment with lipopolysaccharide (LPS) or interleukin-1 (IL-1) significantly increased the number of microglia demonstrating substrate degradation. Substrate-SDS polyacrylamide gel electrophoresis of samples of supernatants from untreated cultured microglia indicated the presence of a 72 and a 92 kD metalloproteinase with characteristics corresponding to collagenases. Supernatants from untreated astrocyte cultures were shown to have primarily a 72 kD metalloproteinase. Proteinase activity increased on stimulation of the microglia with LPS and IL-1 in a dose-dependent fashion. These results indicate that cultured microglia release active proteases capable of degrading the extracellular matrix in a localized region. The production of proteases by activated microglia may have important physiological and pathophysiological consequences within the restricted extracellular matrix of the CNS.

The production of interleukin-1 (IL-1) by cultured neonatal rat microglia was studied using the D10 cell assay. The results show that IL-1 was secreted in response to lipopolysaccharide (LPS) in a dose- and time-dependent fashion. IL-1 production was specific to microglia and was not induced in astrocytes. Indomethacin, which is known to modulate the release of IL-1 from monocytes, had no effect on LPS-stimulated microglia. Aging of the microglia from two weeks to 4 weeks in culture, however, reduced the release of IL-1 in response to LPS. Our data indicate that microglia are a major source of IL-1 and that the release of IL-1 depends on the presence of inflammatory mediators such as LPS and the age of the culture.

Cultured neonatal rat microglia were pretreated with varying doses of either purified interferon (IFN) alpha/beta or recombinant IFN gamma for 24 or 48 h and the following functional parameters examined; superoxide anion production, interleukin-1 secretion and chemotaxis. IFN gamma produced a marked increase in superoxide anion levels when PMA was used to initiate superoxide anion production but had no effect in OPZ-stimulated microglia. Treatment with IFN alpha/beta potentiated superoxide anion production in both PMA and OPZ-stimulated cells. Interleukin-1 activity was decreased by treatment with IFN gamma for 24 h while IFN alpha/beta increased IL-1 activity at 48 h. Removal of serum from the treatment media prevented the action of IFN alpha/beta on IL-1 production. Treatment with IFN alpha/beta or gamma decreased chemotaxis of microglia in response to zymosan activated serum. The data indicate that IFN gamma and alpha/beta can regulate microglial function and that this regulation may differ from that seen for other monocytically derived macrophages.

The production of interleukin-1 (IL-1) was examined in cultured CNS microglia obtained from trisomy 16 (Ts16) fetal mouse brain, a model system for studies relevant to Down syndrome (DS). When compared to microglia from their normal littermates, Ts16 microglia produced significantly higher levels of IL-1 activity both before and following stimulation with lipopolysaccharide (LPS). IL-1 release was stimulated by alpha/beta interferon (IFN) in the normal but not Ts16 microglial cultures. The overall level of IL-1 production in normal littermates, however, was still less than that seen in Ts16. Thus, microglia from Ts16 mice may function in an inappropriate manner and, if this abnormality occurs in vivo, may have wide ranging effects on a developing nervous system.