Treatment for Lupus Skin Lesions

The inflammatory disease lupus affects many organ systems, including renal, cardiovascular, musculoskeletal, and skin. Earlier studies have suggested that skin-specific dendritic cells called Langerhans cells play an important role in skin disease associated with lupus. Dendritic cells are an important link between the innate immune system and the adaptive immune system in that they engulf pathogens, promoting inflammation and presenting the antigens to T cells, which results in further activation of the adaptive immune system.

What Problem Was Studied?
DCB-3503 is a synthetic compound derived from the roots of a plant that has traditionally been used in China and India to treat allergic and inflammatory disorders. This substance has been shown to inhibit the activity of NF-κB, a critical enzyme that promotes the inflammatory response initiated by dendritic cell activation. Because DCB-3503 has shown promise in a rat model of rheumatoid arthritis (see related article), Joseph Craft, MD, of Yale University in New Haven, CT, and his research team decided to investigate it as treatment in a mouse model of lupus.

What Was Done in the Study?
Mice specially bred to develop a lupus-like disease were treated with low-dose DCB-3503, high-dose DCB-3505, cyclophosphamide (active control), or placebo control. Various disease activity and organ function tests were performed on the mice after 8 weeks, 13 weeks and 20 weeks of treatment.

What Were the Study Results?
The investigators found that the mice treated with high doses of DCB-3503 had a significant reduction in skin lesions compared with those receiving placebo control. Cyclophosphamide treatment also resulted in a reduction in skin lesions, but it was less effective than DCB-3503. However, measures of kidney function were no better in the DCB-3503–treated mice compared with the placebo-treated mice. This result indicates the immune system pathway that leads to skin disease in lupus is different from the pathway that leads to kidney disease. Dr. Craft hypothesizes that DCB-3503 may target Langerhans cells in the skin, inhibiting the inflammatory cascade that leads to skin lesions.

What Does This Mean for People With Lupus?
Inflammatory skin disease occurs in up to 70 percent of people with systemic lupus erythematosus. The scarring lesions associated with lupus are particularly difficult to treat. This study in a mouse model of lupus indicates that DCB-3503 nearly eliminates skin disease and may have a role in the treatment of inflammatory skin disease in humans with lupus.

Choi JY, Gao W, Odegard J, et al. Abrogation of skin disease in lupus-prone MRL/Faslpr mice by means of a novel tylophorine analog. Arthritis Rheum 2006;54:3277-83.

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