Inflammation & Allergy-Drug Targets (v.13, #3)

Inflammaging refers to a continuous, low-grade inflammation associated with aging. Such chronicinflammatory response could build up with time and gradually causes tissue damage. It is considered as one of the drivingforces for many age-related diseases such as diabetes, atherosclerosis, age-related macular degeneration (AMD), and skinaging. There is mounting evidence that indicates aging is driven by the pro-inflammatory cytokines and substancesproduced by our body's innate immune system. The macrophage and complement system, two important components ofinnate immune system, have attracted more and more attention since they appear to be involved in the pathogenesis ofseveral inflammaging-associated diseases, such as AMD and atherosclerosis. This paper will review what we know aboutthese two innate immune systems in the pathogenesis of AMD, atherosclerosis and skin aging.

Acne Vulgaris: an Inflammatory Disease Even Before the Onset of Clinical Lesions by Marco Alexandre Rocha, Caroline Sousa Costa, Edileia Bagatin (162-167).
Acne is a chronic self-limited disease, which affects mostly teenagers, without gender difference. In recentyears, the incidence has increased in female adults. The factors involved in this epidemiological observation are still underdiscussion in the literature.;Clinically, acne is characterized by different types of lesions. The disease affects the regions rich in sebaceous glands(face, chest and upper back). The clinical lesions are: open and closed comedones, erythematous papules, pustules,nodules and different types of scars. Taking into consideration the general concept of inflammation (redness, pain, heatand loss of function), acne is traditionally classified as non-inflammatory (open and closed comedones) and inflammatory(other primary lesions). With the knowledge advancement this concept seems to be wrong and therefore acne would be aninflammatory disease even before the onset of their clinical lesions.

Effect of Botanicals on Inflammation and Skin Aging: Analyzing the Evidence by Amanda Suggs, Patricia Oyetakin-White, Elma D. Baron (168-176).
The skin and its immune system manifest a decline in physiologic function as it undergoes aging. Externalinsults such as ultraviolet light exposure cause inflammation, which may enhance skin aging even further leading tocancer and signs of photoaging. There is a potential role for botanicals as an adjunct modality in the prevention of skinaging. Numerous over-the-counter anti-aging products are commercially available, many of which boast unverified claimsto reduce stress, inflammation and correct signs of aging. In this article we reviewed the scientific literature for data onfrequently published “anti-inflammaging” additives such as vitamins A, C and E and green tea. We also analyzed theevidence available on five promising ingredients commonly found in anti-aging products, namely, argan oil, rosemary,pomegranate, Coenzyme Q10, and Coffeeberry. Though there may be an increasing amount of scientific data on a few ofthese novel botanicals, in general, there remains a lack of clinical data to support the anti-aging claims made.

The intricate relationship between stress and skin conditions has been documented since ancient times. Recentclinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, theexact underlying mechanisms have only been studied and partially revealed in the past 20 years or so. In this review, theauthors will discuss the recent discoveries in the field of “Brain-Skin Connection”, summarizing findings from theoverlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology.

Neuromodulatory and Anti-Inflammatory Ingredient for Sensitive Skin: In Vitro Assessment by Adilson Costa, Samara Eberlin, Anelise J. Polettini, Andreia F. da Costa Pereira, Caroline S. Pereira, Nayara M. Cortes Ferreira, Eleonora Dolis, Liliana B. Oliveira Torloni (191-198).
The manifestation of sensitive skin occurs as a consequence of increased permeability of the Stratum corneum,besides the involvement of neuro-immune-endocrine system. In this study, we evaluated the effects of an active ingredientSensC on the production of neuropeptides substance P (SP), enkephalin and β-endorphin; eicosanoids prostaglandin E2(PGE2) and leukotriene B4 (LTB4); histamine, transient receptor potential vanilloid subfamily member 1 (TRPV1), andenvelope proteins filaggrin and involucrin, using an in vitro model of human cell culture. Our results demonstrated thattreatment of keratinocyte cultures with SensC prevented the increase of all evaluated inflammatory mediators induced byinterleukin-1 alpha (IL-1α). As the same way, SensC provides decrease in the synthesis of TRPV1. Regarding thesynthesis of envelope proteins, SensC promoted increases for filaggrin and involucrin levels, when compared to controlgroup. Considering the absence of appropriate treatment, the availability of ingredients, such as SensC, with antiinflammatoryand protective barrier properties can be a significant tool for preventing neurosensorial symptomsassociated with sensitive skin.

Biological Treatments for SAPHO Syndrome: An Update by Davide Firinu, Giuseppe Murgia, Maria Maddalena Lorrai, Maria Pina Barca, Maria Monica Peralta, Paolo Emilio Manconi, Stefano R. del Giacco (199-205).
Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is a rare and often unrecognizeddisease with prominent inflammatory cutaneous and articular manifestations. Since the identification of the syndromemany immunosuppressive drugs have been used for the management of SAPHO, with variable results. The use of anti-TNF-α agents as a therapeutic option for SAPHO cases unresponsive or refractory to conventional drugs, demonstratedtheir efficacy for bone, skin and joints manifestations. TNF-α is a pro-inflammatory cytokine and pivotal regulator ofother cytokines, including IL-1 β , IL-6 and IL-8, involved in inflammation, acute-phase response induction andchemotaxis. IL-1 inhibition strategies with Anakinra have proven their efficacy as first and second line treatment. Weherein review the literature concerning the use of biological drugs in patients with SAPHO syndrome. In addition, wedescribe for the first time the use of Ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure ofmultiple drugs including anti-TNF-α and Anakinra. This anti-IL12/IL23 agent could be a promising therapeutic option,also considering the opportunity to interfere with the IL23/TH17 pathway, which we recently found disturbed.Furthermore, a rationale emerges for the use of the new anti-IL-1 antagonists or the IL-17 blockade, in particular for themost difficult-to-treat SAPHO cases.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune diseases and include dermatomyositis,polymyositis, necrotizing myopathy and inclusion body myositis; they are characterized by inflammation of skeletalmuscle and other internal organs and may potentially lead to irreversible damage and death. Only a small percentage ofIIM has clinically overt cardiac disease; however, heart involvement is one of the leading causes of death and therefore,early detection remains a challenge.;Biochemical markers and non-invasive methods such as the electrocardiogram and echocardiography have a role indiagnosis, but lack sensitivity in identifying patients with early, sublinical cardiac abnormalities. Endomyocardial andskeletal muscle biopsies are very useful, but invasive techniques and cannot be used for routine follow-up. Cardiac andskeletal magnetic resonance imaging, due to their capability to perform tissue characterization, has emerged as noveltechniques for the early detection and follow-up of myocardial and skeletal muscle tissue changes (oedema, inflammation,fibrosis) in IIM. However, the clinical implications of using these approaches and their cost /benefit ratio require furtherevaluation.