Thalidomide inhibits human ultraviolet‐B‐induced skin inflammation?

Criado, Paulo Ricardo; Vasconcellos, Cídia; Omar, Erick D.; Valente, N. Y. S.; Sotto, Mírian Nacagami; Martins, José Eduardo

doi:10.1111/j.1468-3083.2007.02192.x

Cited by 1 publication

(2 citation statements)

References 5 publications

(6 reference statements)

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“…Intriguingly, it has been shown that thalidomide significantly inhibits UV-induced inflammation in human skin (27,28). This may also provide an explanation for the drug's therapeutic effect in photosensitive diseases such as lupus erythematosus (27,28).…”

Section: Discussionmentioning

confidence: 99%

“…This may also provide an explanation for the drug's therapeutic effect in photosensitive diseases such as lupus erythematosus (27,28). As UV-induced inflammation in mice and humans is most likely dependent on IL-1 activity (16,23), this raises the possibility that IL-1Ra may be a useful substitute for thalidomide in the treatment of photosensitive disorders.…”

Section: Discussionmentioning

confidence: 99%

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Thalidomide Inhibits Activation of Caspase-1

Keller

Sollberger

Beer

2009

The Journal of Immunology

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Thalidomide is an efficient anti-inflammatory and anti-angiogenic drug, but its therapeutic use is problematic due to a strong teratogenic activity. Nevertheless, thalidomide was approved for the treatment of inflammatory skin diseases and certain types of cancer, and it is extensively tested for several other indications. Recently, we demonstrated that active caspase-1, whose activation is dependent on inflammasome complexes, is required for unconventional protein secretion of proinflammatory cytokines such as IL-1 and of the proangiogenic fibroblast growth factor 2. In this study, we show that pharmacological doses of thalidomide strongly reduced the secretion of both proteins. Thalidomide-treated cells also released less of other leaderless proteins, which require caspase-1 activity for their secretion. In line with these findings, the drug inhibited activation and activity of caspase-1 in cultured cells but not in vitro. The latter finding suggests that the pharmacological activity is exerted by a metabolite of the drug. The anti-inflammatory activity of thalidomide was also mediated via caspase-1 in mice. These findings represent a novel mechanism by which thalidomide exerts its pharmacological activity and suggest that inhibition of the activity of IL-1 might represent a novel strategy to substitute thalidomide.

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