Coal tar is one of the oldest and an effective treatment for
psoriasis.
Coal tar has been directly applied to the skin, or used in combination with UV light as part of the Goeckerman treatment. The use of
coal tar has caused long-term remissions in
psoriasis, but has fallen out of favor because the treatment requires hospitalization and
coal tar is poorly acceptable aesthetically to patients. Thus, determining the active antipsoriatic component of
coal tar is of considerable therapeutic interest. We fractionated
coal tar into its components, and tested them using the SVR
angiogenesis inhibitor assay. Treatment of SVR endothelial cells with
coal tar fractions resulted in the isolation of a single fraction with antiangiogenic activity. The active antiangiogenic compound in
coal tar is
carbazole. In addition to antiangiogenic activity,
carbazole inhibited the production of inflammatory
IL-15 by human mononuclear cells.
IL-15 is elevated in
psoriasis and is thought to contribute to psoriatic
inflammation.
Carbazole treatment also reduced activity of
inducible nitric oxide synthase (iNOS), which is proinflammatory and elevated in
psoriasis. The effect of
carbazole on upstream pathways in human
psoriasis was determined, and
carbazole was shown to inhibit signal transducer and activator of transcription (stat)3-mediated transcription, which has been shown to be relevant in human
psoriasis.
IL-15, iNOS, and stat3 activation require the activation of the
small GTPase rac for optimal activity.
Carbazole was found to inhibit rac activation as a mechanism for its inhibition of downstream inflammatory and angiogenic pathways. Given its antiangiogenic and anti-inflammatory activities,
carbazole is likely a major component of the antipsoriatic activity of
coal tar.
Carbazole and derivatives may be useful in the
therapy of human
psoriasis.