Acne pathogenesis: Researchers focus on elucidating role of TNF-alpha in inflammatory pathways

November 1, 2008

Tissue necrosis factor-alpha (TNF-alpha) is a pivotal cytokine in inflammatory pathways, but its role in acne has not been characterized. Studies under way at the University of Miami Miller School of Medicine aim to elucidate more information with the ultimate goal of identifying potential new therapeutic targets for acne.

Key Points

Miami - Confirmation that tissue necrosis factor-alpha (TNF-alpha) is detectable in both inflammatory and noninflammatory lesions of acne patients suggests that further studies are warranted to investigate the role of this cytokine in acne pathogenesis and how it is affected by acne treatments, according to researchers from the University of Miami Miller School of Medicine.

Results were presented from a study determining levels of TNF-alpha in inflammatory and noninflammatory acne comedones of six acne patients, including two treated with oral trimethoprim/sulfamethoxazole (TMP/SMX).

METHODOLOGY

The lesion samples were weighed, normalized to a standard concentration of acneiform material and then homogenized for analysis of TNF-alpha concentration using an enzyme-linked immunoabsorbent assay (ELISA).

RESULTS

Results showed that TNF-alpha was detectable in all acne lesions. However, there were no significant differences comparing concentrations of the cytokine between inflammatory and noninflammatory lesions in TMP/SMX-treated or untreated patients, nor did TMP/SMX treatment significantly reduce levels of TNF-alpha in inflammatory or noninflammatory lesions.

"The good news is that using our methodology, we were able to detect TNF-alpha in both clinically inflammatory and noninflammatory open-comedone acne lesions. We believe our inability to detect a higher level of TNF-alpha in the inflammatory lesions compared with the noninflammatory lesions may be due to our limited sample size," says Ran Huo, B.S.

"Small sample size may also account for the results showing that treatment with TMP/SMX failed to significantly reduce TNF-alpha levels in the acne lesions," Mr. Huo adds. "While, to our knowledge, this antibiotic has no direct anti-inflammatory properties, because it inhibits Propionibacterium acnes and since P. acnes has been shown in vitro to directly increase production of TNF-alpha by macrophages, keratinocytes and fibroblasts, we expected to see a treatment effect."

Mr. Huo is a dermatology research fellow working under Brian Berman, M.D., Ph.D., professor of dermatology and internal medicine, University of Miami Miller School of Medicine.

EXPANDING RESEARCH

The team is now expanding research to investigate the effect of antibiotics with anti-inflammatory effects, such as macrolides and tetracyclines, on TNF-alpha levels in acne comedone lesions.

"Having detected a baseline level of TNF-alpha, if agents known to be beneficial in acne are found to decrease levels of this pro-inflammatory cytokine, therapeutic agents targeting TNF-alpha may add to the (armamentarium) of treatment options for this very common dermatologic disease," Mr. Huo says.

This difference might have confounded the results, since the TMP/SMX-treated patients might have had higher levels of inflammatory mediators, including TNF-alpha.

MEDIATORS

"It would be interesting to evaluate levels of other inflammatory mediators as well, and to see how they are affected by antimicrobials and the various topical agents used to treat acne," says Dr. Berson, assistant professor of dermatology, Weill Medical College of Cornell University, New York.

She also says this research highlights the increasing attention being directed to the role of inflammation as a pathogenic factor in acne.

"Inflammation is involved not only in the development of inflammatory lesions, but also affects comedogenesis.

"The message we have to keep in mind is that treatment with antibiotics at doses with antimicrobial activity targets bacteria, but not necessarily inflammation.

"Use of subantimicrobial doses that have anti-inflammatory effects may turn out more or equally important for treating acne than bacterial eradication," Dr. Berson adds.

Disclosures: Dr. Berson is a consultant for Collagenex and Medicis, companies that market antibiotics used in the treatment of acne. Dr. Berman and Mr. Huo report no relevant financial interests.

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