BACKGROUND: Systemic lupus erythematosus (SLE) is still treated with global immunosuppressants with serious toxicities. We hypothesized that endogenous immunosuppressive molecules might be able to control SLE manifestations more specifically. Heat shock protein 10, or chaperonin 10 (Cpn10), is a secretory molecule that can suppress innate and adaptive immunity. METHODS: Recombinant human Cpn10 (100 μg per mouse) was given intraperitoneally to healthy-appearing female MRL-(Fas)lpr mice from 12 to 22 weeks of age. At the age of 22 weeks, mice were analysed for treatment outcome by harvesting organs, plasma and urine. RESULTS: Cpn10 entirely prevented cutaneous lupus lesions as compared to vehicle-treated mice. Cpn10 also suppressed lupus nephritis as evident from serum creatinine levels, albuminuria and the scores of disease activity and chronicity. Autoimmune lung disease was unaffected by Cpn10 treatment while overall survival of mice was prolonged. Cpn10 did not have any major effects on either dendritic cell or B-cell counts except T cells in spleen, plasma interferon-gamma, tumour necrosis factor-alpha, interleukin-10, anti-nuclear autoantibody levels or markers of lymphoproliferation. CONCLUSIONS: In summary, recombinant Cpn10 selectively prevents cutaneous lupus and suppresses nephritis in MRL-(Fas)lpr mice without affecting the underlying systemic autoimmune process. Hence, Cpn10 might be useful for the treatment of skin and kidney manifestations of SLE.
BACKGROUND: Systemic lupus erythematosus (SLE) is still treated with global immunosuppressants with serious toxicities. We hypothesized that endogenous immunosuppressive molecules might be able to control SLE manifestations more specifically. Heat shock protein 10, or chaperonin 10 (Cpn10), is a secretory molecule that can suppress innate and adaptive immunity. METHODS: Recombinant humanCpn10 (100 μg per mouse) was given intraperitoneally to healthy-appearing female MRL-(Fas)lpr mice from 12 to 22 weeks of age. At the age of 22 weeks, mice were analysed for treatment outcome by harvesting organs, plasma and urine. RESULTS:Cpn10 entirely prevented cutaneous lupus lesions as compared to vehicle-treated mice. Cpn10 also suppressed lupus nephritis as evident from serum creatinine levels, albuminuria and the scores of disease activity and chronicity. Autoimmune lung disease was unaffected by Cpn10 treatment while overall survival of mice was prolonged. Cpn10 did not have any major effects on either dendritic cell or B-cell counts except T cells in spleen, plasma interferon-gamma, tumour necrosis factor-alpha, interleukin-10, anti-nuclear autoantibody levels or markers of lymphoproliferation. CONCLUSIONS: In summary, recombinant Cpn10 selectively prevents cutaneous lupus and suppresses nephritis in MRL-(Fas)lpr mice without affecting the underlying systemic autoimmune process. Hence, Cpn10 might be useful for the treatment of skin and kidney manifestations of SLE.
Authors: Masayuki Mizui; Tomohiro Koga; Linda A Lieberman; Jessica Beltran; Nobuya Yoshida; Mark C Johnson; Roland Tisch; George C Tsokos Journal: J Immunol Date: 2014-07-25 Impact factor: 5.422