TABLE 1.

Summary of evidence for early inflammatory events during acne lesion development

INCREASED EXPRESSION AND BIOACTIVITY OF PROINFLAMMATORY MEDIATORS

Upregulation of inflammatory mediators in uninvolved skin and early lesions3,4 - E-selectin - Vascular adhesion molecule-1 - Interleukin-1 - Integrin Interleukin-1α bioactivity in open comedones5 Upregulation of defensin-2 immunoreactivity6,7 Elevation of CD3+ and CD4+ T cells and macrophages in uninvolved skin3

PEPTIDASES

Expression of proinflammatory peptidases on sebocytes and keratinocytes8 Inhibition of peptidase activity leads to an anti-inflammatory profile8,9

NEUROPEPTIDES

Upregulation of neuropeptides in uninvolved skin10,11 - Corticotropin-releasing hormone - Melanocortin-1 receptor - Substance P

TOLL-LIKE RECEPTORS

Activation by Propionibacterium acnes triggers inflammatory cytokine responses12,13 - P. acnes is present in sebaceous follicles undergoing comedogenesis and may play a role in comedo formation14,15 Activation by endogenous ligands?16

CHANGES IN LIPID BIOSYNTHESIS

Confirmed association between sebaceous lipid synthesis and inflammation17,18 Peroxidated lipids trigger inflammatory responses19

CLINICAL TRIALS

The anti-inflammatory dapsone is effective in treatment of “noninflammatory” lesions20,21 - Dapsone has multiple anti-inflammatory properties22,25 Retinoids are effective in treating “noninflammatory” lesions26 - Retinoids downregulate toll-like receptor-2 and interleukin-10 expression27,28