Acne is a disease unique to humans. It affects up to 80 % of young adults, in whom it can induce stress, depression, and anxiety, as determined by psychometric scoring (47,111,112). Acne is a disease of the infundibulum or "pore" of the human sebaceous pilosebaceous unit and of the gland itself. This unit develops at puberty, appears only at the site of acne lesions (the chest, back, and face), and seems to have no other function than to sometimes produce acne lesions. The earlier forms of acne are characterized by microcomedones, which represent an intrainfundibular scaling-like phenomenon. As the disease progresses in severity, comedogenesis develops, as does inflammation. Duct rupture is a late event in the development of most inflammatory lesions (47-50).

Acne is generally accepted by clinicians to be a multifactorial disease and it is believed that acne is associated with seborrhea, the excess production of sebum by the sebaceous gland (49,113). Further, Propionibacferinm acnes is a major bacterium implicated in the pathogenesis of acne (114). Acne is characterized by the presence of noninflammatory lesions, termed comedones (47,50). The earliest pathological change in acne is altered follicular epithelial differentiation, resulting in a follicular retention hyperkeratosis—the microcomedo (50). In addition to the noninflammatory lesions, inflammatory lesions can develop when such microcomedos are colonized by P. acnes. For inflammatory lesions such as papules, pustules, and nodulocystic lesions to occur, a variety of pathogenic factors are involved, including besides P. acnes, inflammatory mediators, and host immunity (115). In vitro experiments on organ maintained human infudibula have identified a number of cyto-kines that can model the morphological and inflammatory aspects of acne (116). These cytokines not only induce the infundibular changes in acne, namely (i) hyper-cornification (scaling) of the infundibulum, (ii) expression of intercellular adhesion molecule-1 and human leukocyte antigen-D related, and (iii) disruption of infundibular morphology, but will also inhibit the secretion of lipid from the sebaceous gland (117). Since acne seems to be provoked by P. acnes in sebum and since P. acnes depends on sebum for nutrition, the inhibition of sebum secretion would be expected to promote the remission of the disease by inhibiting P. acnes colonization (117).

A number of acne therapies are currently in use, including retinoids (e.g., isotretinoin, adapalene), antiandrogens (e.g., cyproterone acetate), contraceptives, antibacterials (e.g., clindamycin, erythromycin), benzoyl peroxide, and salicylic acid (118,119). In milder cases, topical therapy is sufficient, but in more severe

TABLE 3 Summary of Peroxisome Proliferator Activated Receptor Expression Profiles and Physiological Functions in Various Study Models

Study model

PPAR expression profiles

Physiological functions upon subtype activation

Rodent epidermis in vitro

Human epidermis in vitro Rodent keratinocytes in vitro

Human keratinocytes in vitro

Murine hair follicles Mutant mouse models

Human hair follicles

Rat sebocytes in vitro

Human sebocytes in vitro

Hamster sebaceous gland in vitro Human sebaceous gland in vitro

Human clinical data in vivo

PPARa = PPARa/S = PPARy in fetal epidermis, not present in the adult PPARa/S » PPARa = PPARy PPARa = PPARa/S = PPARy


PPARa not determined PPARa = PPARa/S = PPARy

Not determined

PPARa/S > PPARa = PPARy Not determined

PPARa: acceleration of epidermal maturation PPARa/S and PPARy: no effects

Not determined

PPARa: induction of differentiation PPARa/S and PPARy: no effects

PPARa: regulation of lipid metabolism, possible induction of differentiation and inhibition of proliferation PPARa/S: induction of differentiation PPARy: no effects

Not determined

PPARa and PPARa/S: promote rapid epithelialization of skin wound PPARa: involved in early inflammatory phase of healing PPARa/S: contol of keratinocyte proliferation

PPARa: enhanced hair follicle survival PPARa/S and PPARy: not determined

PPARa, PPARa/S, and PPARy: induction of sebocyte lipogenesis

PPARa/S: stimulation of lipid synthesis PPARa and PPARy: no effects

PPARa: inhibition of lipid synthesis PPARa/S and PPARy: not determined

PPARa, PPARa/S, and PPARy: inhibition of lipid sythesis

PPARa: inhibition of sebum secretion PPARa/S and PPARy: not determined

Abbreviation-. PPAR, peroxisome proliferator activated receptor.

cases where papulopustular or nodulocystic acne is present, there is a need of systemic treatment. However, there is a continued need for effective drugs for the therapy of acne, although judicious combined use of existing topical and systemic therapies offers great relief to many patients and a recent review of these therapies indicated that approximately 68% of treatment is effective (120). Nonetheless, PPARs may offer a solution for the development of novel effective drugs for acne therapy.

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Relieving Your Life of Acne

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