Innovative strategies for the discovery of new drugs against alopecia areata: taking aim at the immune system.

INTRODUCTION: The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored. AREAS COVERED: This review summarizes key AA disease mechanisms, current therapeutic methods, and emerging treatments, including Janus Kinase (JAK) inhibitors. The authors determine that innovative drug discovery strategies for AA are still needed due to continued unmet medical needs and the limited efficacy of current and emerging therapeutics. For prospective AA treatment developers, the authors identify the pre-clinical disease models available, their advantages, and limitations. Further, they outline treatment development opportunities that remain largely unmapped. EXPERT OPINION: While recent advancements in AA therapeutics are promising, challenges remain, including the lack of consistent treatment efficacy, long-term use and safety issues, drug costs, and patient compliance. Future drug development research should focus on patient stratification utilizing robust biomarkers of AA disease activity and improved quantification of treatment response. Investigating superior modes of drug application and developing combination therapies may further improve outcomes. Spirited innovation will be needed to advance more effective treatments for AA.

Alopecia areata (AA) is an autoimmune condition that causes hair loss. It significantly affects a patient's emotional well-being and quality of life. Companies, clinics, and researchers are working hard to understand AA and create better treatments. Despite these efforts, there are still many unanswered questions, and new treatment methods still need to be explored.This review summarizes how AA develops, current treatment options, and new therapies like Janus Kinase (JAK) inhibitor drugs. JAK inhibitors show promise, but they are not fully effective for everyone. We emphasize that there is still a need for new and innovative drug discovery strategies to meet the medical needs of AA patients, as current treatments often fall short.For researchers and developers of AA treatments, we discuss the available pre-clinical models used to test new drugs, highlighting their strengths and weaknesses. We also point out new areas for treatment development that have not been thoroughly investigated.Although recent advancements in AA treatments are encouraging, several challenges remain. These include inconsistent effectiveness of treatments, safety concerns with long-term use, high drug costs, and issues with patient adherence to treatment programs. We believe future research should focus on identifying biomarkers that can help tailor treatments to individual patients and improving measurements of treatment success. Additionally, exploring better ways to apply drugs and combining different therapies together may enhance treatment outcomes.Ultimately, innovative approaches and spirited efforts will be required to develop more effective treatments for AA to improve the lives of those affected by this challenging condition.

Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Current Protocols: Alopecia Areata Mouse Models for Drug Efficacy and Mechanism Studies.

Alopecia areata is the second most common form of hair loss in humans after androgenetic alopecia. Although a variety of animal models for alopecia areata have been described, currently the C3H/HeJ mouse model is the most commonly used and accepted. Spontaneous hair loss occurs in 15%-25% of older mice in which the lesions wax and wane, similar to the human disease, with alopecia being more common and severe in female mice. Full-thickness skin grafts from mice with spontaneous alopecia areata to young, normal-haired, histocompatible mice provide a highly reproducible model with progressive lesions that makes it useful for drug efficacy and mechanism-based studies. As alopecia areata is a cell-mediated autoimmune disease, transfer of cultured lymph node cells from affected mice to unaffected, histocompatible recipients also promotes disease development and provides an alternative, nonsurgical protocol. Protocols are presented to produce these models such that they can be used to study alopecia areata and to develop novel drug therapies. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Full-thickness skin grafts to reproducibly induce alopecia areata in C3H/HeJ mice Basic Protocol 2: Adoptive transfer of cultured lymphoid cells provides a nonsurgical method to induce alopecia areata in C3H/HeJ mice.

Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Allergen desensitization reduces the severity of relapsed alopecia areata in dust-mite allergic patients.

Atopy may be a facilitating factor in some alopecia areata (AA) patients with early disease onset and more severe/extensive AA. The underlying immune mechanisms are unknown, but allergen responses may support a pro-inflammatory environment that indirectly promotes AA. To investigate the long-term effect of allergen immunotherapy (AIT) against house dust mite (HDM) allergy on disease severity and prognosis for AA patients. An observational comparative effectiveness study was conducted on 69 AA patients with HDM allergy. 34 patients received conventional/traditional AA treatment (TrAA) plus AIT (AIT-TrAA), and 35 patients received TrAA alone. Serum total immunoglobulin E (tIgE), HDM specific IgE (sIgE), HDM specific IgG4 (sIgG4) and cytokines (IL-4, IL-5, IL-10, IL-12, IL-13, IL-33, IFNγ) were quantified in these patients, together with 58 non-allergic AA patients and 40 healthy controls. At the end of the 3-year desensitization course, the AIT-TrAA group presented with lower SALT scores than the TrAA group, especially in non-alopecia totalis/universalis (AT/U) patients and pre-adolescent AT/U patients (age ≤ 14). In patients with elevated tIgE levels before AIT, a decrease in tIgE was correlated to reduced extent of AA on completion of the AIT course. After desensitization, elevation of IL-5 and decrease of IL-33 were observed in HDM allergic-AA patients. Desensitization to HDM in allergic AA patients reduces the severity of relapse-related hair loss over the 3-year AIT treatment course, possibly via opposing Th2 dominance. This adjunctive treatment may help reduce disease severity and curtail the disease process in allergic patients with AA.

Nonsurgical Induction of Alopecia Areata in C3H/HeJ Mice via Adoptive Transfer of Cultured Lymphoid Cells.

Surgical induction of alopecia areata (AA) via full-thickness grafting of spontaneous AA-affected C3H/HeJ mouse skin to naïve recipients has been a primary method of transferring the AA disease model phenotype. However, this method is associated with the need to perform an invasive procedure that could negatively impact animal wellbeing. Therefore, a rodent model that rapidly develops AA at a predictable rate and without the need to perform invasive surgical procedures on the mice is essential for studying the pathogenesis of AA. Here we describe a cell injection technique using cultured skin-draining lymph node cells (LNCs) injected intradermally into naïve recipients to induce rapid AA development. The cultured LNCs can reach ~ten fold expansion after 6 days with specific cytokine stimulation. The LNCs derived from a single AA affected mouse donor can induce AA development in more than 80 naïve mice within 2-18 weeks. For comparative control studies, mice receiving cultured LNCs from normal donors remain normally haired. The method enables the production of large numbers of AA mice for use in research and treatment development studies while avoiding the use of surgical procedures. We anticipate that the protocol can also be adapted for use in other mouse autoimmune disease models.

Growth factor concentrations in platelet-rich plasma for androgenetic alopecia: An intra-subject, randomized, blinded, placebo-controlled, pilot study.

BACKGROUND: Platelet-rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). OBJECTIVE: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo-controlled, pilot clinical trial (NCT02074943). METHODS: The efficacy of an 8 week, five session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated with the growth factor concentrations in PRP. RESULTS: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46%, respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (P = .004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. LIMITATIONS: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. CONCLUSIONS: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors postprocessing might improve hair growth responses.

A "hair-raising" history of alopecia areata.

A 3500-year-old papyrus from ancient Egypt provides a list of treatments for many diseases including "bite hair loss," most likely alopecia areata (AA). The treatment of AA remained largely unchanged for over 1500 years. In 30 CE, Celsus described AA presenting as scalp alopecia in spots or the "windings of a snake" and suggested treatment with caustic compounds and scarification. The first "modern" description of AA came in 1813, though treatment still largely employed caustic agents. From the mid-19th century onwards, various hypotheses of AA development were put forward including infectious microbes (1843), nerve defects (1858), physical trauma and psychological stress (1881), focal inflammation (1891), diseased teeth (1902), toxins (1912) and endocrine disorders (1913). The 1950s brought new treatment developments with the first use of corticosteroid compounds (1952), and the first suggestion that AA was an autoimmune disease (1958). Research progressively shifted towards identifying hair follicle-specific autoantibodies (1995). The potential role of lymphocytes in AA was made implicit with immunohistological studies (1980s). However, studies confirming their functional role were not published until the development of rodent models (1990s). Genetic studies, particularly genome-wide association studies, have now come to the forefront and open up a new era of AA investigation (2000s). Today, AA research is actively focused on genetics, the microbiome, dietary modulators, the role of atopy, immune cell types in AA pathogenesis, primary antigenic targets, mechanisms by which immune cells influence hair growth, and of course the development of new treatments based on these discoveries.

Serum level of IL-4 predicts response to topical immunotherapy with diphenylcyclopropenone in alopecia areata.

BACKGROUND: This study investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). OBJECTIVE: To identify predictors of response, or resistance, to treatment for AA through clinical observations and serum tests. METHODS: Eighty four AA patients were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays. RESULTS: Of patients, 56.1% responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07 fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels. LIMITATIONS: A small number of subjects were evaluated. CONCLUSIONS: Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA.

Allergy promotes alopecia areata in a subset of patients.

In this commentary, we focus on allergy as a facilitating factor in the pathogenesis of alopecia areata (AA). From previous studies on AA, it is well known that subsets of patients can have one or more of; seasonal relapse, comorbid atopic rhinitis, asthma and dermatitis, lesion infiltrating eosinophils and plasma cells, high levels of total IgE, specific IgE for house dust mites (HDMs), and/or disrupted skin barrier function by the evaluation of filaggrin. Allergy and AA share a similar genetic background; both contributing to an immune reaction imbalance. Furthermore, adjunctive treatment with antihistamines, or desensitization for HDM, can reduce the severity of alopecia in atopic AA patients. Therefore, allergies may contribute to the onset and relapse of AA. Identification of an allergic or atopic immune component in AA patient subsets may indicate adjunctive treatment intervention measures against allergies should be taken which may improve the success of conventional AA treatment.

Sequential cyclic changes of hair roots revealed by dermoscopy demonstrate a progressive mechanism of diffuse alopecia areata over time.

BACKGROUND: Diffuse alopecia areata (DAA) often leads to a complete hair shedding within a few months. OBJECTIVE: To explore features and mechanisms underlying DAA. MATERIALS AND METHODS: Scalp and hair root dermoscopy were conducted on 23 DAA patients throughout the disease process, 20 patchy Alopecia areata patients, 23 acute telogen effluvium (ATE) patients and 10 normal controls. Histopathology was also evaluated. RESULTS: We found almost all hair roots were anagen in early stage DAA in 18 patients (18/23, 78.3%) within the first 4-8 weeks after hair loss onset. Anagen effluvium (~4 weeks) was followed by catagen (~4 weeks) and then telogen/exogen (~8 weeks) effluvium with overlap. Hair root and proximal hair shaft depigmentation was more prominent in later DAA disease stages. Black dots, exclamation mark hairs and inconsistent thickness of hair shafts were found more often in early than later DAA (Ps < 0.01). Early DAA histopathology revealed more prominent inflammation and hair follicle regression than that observed in the later stages. Patchy alopecia areata patients showed mixed anagen, catagen and telogen hair roots while ATE patients showed increased exogen and mildly decreased hair root pigmentation. CONCLUSION: Sequential cyclic staging of shed hairs in DAA indicates the insult may be hair-cycle specific. We suggest that DAA is initially an anagen effluvium disease involving an intense inflammatory insult, later progressing to a brief catagen effluvium, and then to telogen effluvium with premature exogen, in later stages of DAA.

Increased expression of TLR7 and TLR9 in alopecia areata.

Alopecia areata (AA) is thought to be an autoimmune process. In other autoimmune diseases, the innate immune system and Toll-like receptors (TLRs) can play a significant role. Expression of TLR7, TLR9 and associated inducible genes was evaluated by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals and 19 AA patients, categorized according to disease duration, activity and hair loss extent. Microdissected scalp biopsies from five patients and four controls were also assessed by quantitative PCR and immunohistology. TLR9 was significantly upregulated 2.37 fold in AA PBMCs. Notably, TLR9 was most significantly upregulated in patients with active AA, as shown by a positive hair pull test, compared to stable AA patients. In hair follicle bulbs from AA patients, IFNG and TLR7 exhibited statistically significant 3.85 and 2.70 fold increases in mRNA, respectively. Immunohistology revealed TLR7 present in lesional follicles, while TLR9 positive cells were primarily observed peri-bulbar to AA affected hair follicles. The increased expression of TLR7 and TLR9 suggest components of the innate immune system may be active in AA pathogenesis.

Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model.

Alopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60-70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.

Alopecia Areata is Associated with Increased Expression of Heart Disease Biomarker Cardiac Troponin I.

The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and C-reactive protein, in alopecia areata and androgenetic alopecia affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p <0.05). Alopecia areata subjects not receiving treatments had highest levels of cTnI (p <0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate.

Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis.

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non­follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self­renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

Identification of Autoantigen Epitopes in Alopecia Areata.

Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.

Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma.

UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.

Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51×faster), ostrich oil (1.46×faster), and rhea oil (1.64×faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35×slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions.

Biology of the hair follicle and mechanisms of nonscarring and scarring alopecia.

There are many hair disorders, all of which involve alterations in normal hair biology. Essentially, hair disorders involve changes to hair fiber caliber, density per unit area, and/or the duration of anagen and telogen in the hair growth cycle. Hair disorders may be triggered by inflammation, genetics, the environment, or hormones; the relative contributions of these factors vary for different hair disorder diagnoses. Suitable treatments may either address the underlying causal factors or directly act on hair follicle biology. The objectives are to normalize the hair growth cycle, modulate the size of hair follicles, and potentially regenerate hair follicles to stabilize hair density. The purpose of this manuscript is to review the basic biology of the hair follicle, as well as causal mechanisms for the disordered hair follicle using some selected examples of hair disorders.