Scientists have discovered that the root biochemial cause of acne is not bacteria, but a non specific inflammatory response of our innate immune system to a stimulus.

Inflammatory Events Are Involved in Acne Lesion Initiation - Journal of Investigative Dermatology (2003) 121, 20–27. Anthony HT Jeremy, Diana B Holland, Susan G Roberts, Kathryn F Thomson and William J Cunliffe. Department of Dermatology, University of Leeds, and Leeds General Infirmary, Leeds, UK

The stimulus is a deficiency of essential fatty acids (linoleic acid) in the sebum glands because of a dilution effect of high sebum production. This leads to a perturbation of the barrier function within individual follicles and induces the release of small soluble proteins known as pro-inflammatory cytokines (ie., interlukin (IL-1), tumor necrosis factor) from keratinocytes.

Those cells release these proteins into the dermis to act as intercellular mediators or messangers (cytokines are like alphabet letters that combine to spell words which make up a molecular language). Cytokines generate an inflammatory cascade that leads to connective tissue destruction by stimulating the production of prostaglandins (hormone-like substances derived from arachidonic acid) and collagenase enzymes. Inflammatory events occur prior to and act as causal factors in the hyperproliferative changes observed in acne lesions, as opposed to secondary consequential events.

Thus, acne vulgaris should be classified as an inflammatory skin disorder as opposed to a keratinocyte / hyperproliferative disorder.

The study also provides good evidence to support the treatment of uninvolved skin in acne patients and not just the visible lesions alone and validates the topical use of anti-inflammatory based therapies for this skin disorder.

One of the characteristics leading to the development of an acne lesion is hypercornification of the follicle wall. The follicle walls of the inner funnel shaped section of comedones possess a thicker cornified layer. The composite cells of this layer have thickened cell membranes and their cellular integrity is maintained with many layers of keratinized cells compacted together, which are sloughed off as such.

This is dissimilar to the nature of these cells found in normal follicles, which lose their integrity and are sloughed off as single or smaller groups of cells. This hypercornification gives rise to the "horny" plug, which is formed within the follicular duct/lumen.

Although persons with acne have consistently been observed to have elevated levels of sebum secretion, no mechanism relating sebum secretion rates to comedogenesis is known.

Acne patients have also been shown to have low levels of linoleic acid in their skin surface lipids. To explain this observation, the hypothesis is advanced that the linoleate concentration in human sebum depends on the quantity of linoleic acid present in each sebaceous cell at the commencement of its differentiation and on the extent to which this initial charge is diluted by subsequent endogenous lipid synthesis in each sebaceous cell.

A corollary hypothesis holds that low concentrations of linoleate in sebum impose a state of essential fatty acid deficiency on the cells of the follicular epithelium and induce the characteristic response of hyperkeratosis.

Both hypotheses could hold, without there being a systemic deficiency of linoleic acid, simply as the result of elevated lipogenesis in individual sebaceous cells. Essential fatty acids and acne. J American Academy of Dermatology. 1986 Feb;14(2 Pt 1):221-5.

In wound healing and many pathologic conditions, keratinocytes become activated: they turn into migratory, hyperproliferative cells that produce and secrete extracellular matrix components and signaling polypeptides. At the same time, their cytoskeleton is also altered by the production of specific keratin proteins.

These changes are orchestrated by growth factors, chemokines, and cytokines produced by keratinocytes and other cutaneous cell types. The responding intracellular signaling pathways activate transcription factors that regulate expression of keratin genes. Analysis of these processes led us to propose the existence of a keratinocyte activation cycle, in which the cells first become activated by the release of IL-1.

Subsequently, they maintain the activated state by autocrine production of proinflammatory and proliferative signals. Keratins K6 and K16 are markers of the active state. Signals from the lymphocytes, in the form of Interferon-gamma, induce the expression of K17 and make keratinocytes contractile. This enables the keratinocytes to shrink the provisional fibronectin-rich basement membrane. Signals from the fibroblasts, in the form of TGF-beta, induce the expression of K5 and K14, revert the keratinocytes to the healthy basal phenotype, and thus complete the activation cycle.

Keratins and the Keratinocyte Activation Cycle - Journal of Investigative Dermatology (2001) 116, 633–640