Inflammation and Acne: Putting the Pieces Together

Acne vulgaris affects 40 to 50 million people in the United States and is the most common skin disease treated by physicians.^1-3 Peak incidence occurs during adolescence, affecting approximately 85% of individuals between the ages of 12 and 24 years.³ Furthermore, acne vulgaris continues into the mid-forties in 12% of women and 3% of men.^4-6 Acne lesion progression has long been thought to begin with the formation of the microcomedone, which subsequently would progress into either a noninflammatory or inflammatory lesion. Recent data suggest that inflammation plays a unique role in every stage of the acne life cycle including acne resolution and scarring.^7,8 It is understood that in clinically normal skin, immune cells and inflammatory mediators are present. Changes in hormones, sebum production, desquamation, and P acnes colonization alter the skin microenvironment resulting in a cascade of inflammatory events that promote lesion progression.^9,10 The objective of this review is to first provide a detailed look at inflammation, the cell types that mediate it, and the molecular signaling pathways that perpetuate it. Second, it is to demonstrate how these inflammatory mediators work together to promote acne pathogenesis.

Cytokines and chemokines
Cytokines are a structurally diverse set of proteins that are paramount in modulating the innate and adaptive immune response. Cytokines regulate cell activation, proliferation, hematopoiesis, survival, and migration of leukocytes and are produced by a variety of different cell types including, epithelial cells, macrophages, and CD4 and CD8 T cells.¹¹ Cytokines are typically classified as either proinflammatory, such as interferon (INF)-γ, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-17, or anti-inflammatory, which include IL-4, IL-10, IL-11, and IL-1 receptor antagonist (ra). In acute inflammatory conditions, these mediators are present for short periods of time, typically in response to bacterial or viral stimuli. It is through a negative feedback loop initiated by the production of anti-inflammatory cytokines that proinflammatory cytokine levels return to baseline. In chronic inflammatory conditions, there are an imbalance of proinflammatory cytokines produced and the anti-inflammatory cytokines fail to attenuate the inflammation resulting in a myriad of deleterious effects.¹²

A subset of cytokines that are also released as part of the immune response are called chemokines. Chemokines are small proteins produced by a variety of cell types that function to recruit monocytes/macrophages, neutrophils, and T cells from the circulation to areas of infection. They have been shown to effect the recruitment of T helper (Th) cell subsets through binding of specific chemokine receptors present on the cell surface.¹² Th1 cells preferentially express chemokines receptors, CCR5, and CXCR3 while Th2 cells preferentially express CCR3, CCR4, and CCR8.¹²

T cells play an essential role in immunity through their role as both regulators and effectors of the adaptive immune response. T lymphocytes are white blood cells that mature in the thymus and migrate to the periphery where they differentiate into specific T cell subsets. Antigen specific receptors are located on the cell surface of T lymphocytes and function to recognize foreign pathogens. The two subsets of T lymphocytes are distinguished by the presence of cell surface molecules known as CD4 and CD8.¹³ CD8 T cells or cytotoxic T cells directly target infected