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5-Lipoxygenase activation in psoriasis: a dead issue?
1Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Dorval, Que., Canada.
Skin Pharmacology : the Official Journal of the Skin Pharmacology Society
|January 1, 1993
Summary
5-lipoxygenase activation is not a significant factor in psoriasis. Therefore, drugs that inhibit leukotriene biosynthesis are unlikely to be effective treatments for this skin condition.
Area of Science:
- Dermatology
- Inflammation Research
- Biochemistry
Background:
- Psoriasis involves neutrophil activation and leukotriene B4 presence in lesions.
- 5-lipoxygenase (5-LO) and its inhibitors were hypothesized to be relevant to psoriasis pathology.
Purpose of the Study:
- To critically evaluate the proposed role of 5-lipoxygenase activation in psoriasis pathogenesis.
- To assess the therapeutic potential of 5-lipoxygenase inhibitors in psoriasis treatment.
Main Methods:
- Review of existing literature on 5-lipoxygenase, leukotriene B4, and psoriasis.
- Analysis of the stereochemistry of leukotriene B4-like material in psoriatic skin.
- Evaluation of evidence for 5-lipoxygenase presence in human skin.
- Assessment of the mechanisms of action for drugs used in psoriasis treatment.
Main Results:
- Evidence for 5-lipoxygenase-derived leukotriene B4 in psoriasis is inconclusive due to unconfirmed stereochemistry.
- Convincing evidence for 5-lipoxygenase enzyme presence in human skin is lacking.
- Psoriasis drugs with purported 5-LO inhibitory effects may act via alternative mechanisms.
- Selective leukotriene biosynthesis inhibitors have shown no demonstrated therapeutic utility in psoriasis.
Conclusions:
- 5-lipoxygenase activation is not a significant contributor to psoriasis pathology.
- Selective leukotriene biosynthesis inhibitors are unlikely to offer therapeutic benefits for psoriasis.