Retinoic acid reduces autoimmune renal injury and increases survival in NZB/W F1 mice.
Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent antiproliferative and anti-inflammatory properties. Recently, retinoic acids were reported to inhibit Th1 cytokine production. We investigated the effects of retinoic acid on lupus nephritis in a model of NZB/NZW F(1) (NZB/W F(1)) mice. Three-month-old NZB/W F(1) mice were separated into two groups: one treated with all-trans-retinoic acid (ATRA; 0.5 mg i.p., three times weekly for 7 mo) and one with saline as a control. Compared with controls, ATRA-treated mice survived longer and exhibited a significant reduction of proteinuria, renal pathological findings including glomerular IgG deposits, and serum anti-DNA Abs. Splenomegaly was less marked in the treated mice than in controls. Transcripts encoding IFN-gamma, IL-2, and IL-10 in splenic CD4(+) T cells were significantly reduced in treated mice compared with controls. We conclude that treatment with ATRA in SLE-prone NZB/W F(1) mice significantly alleviates autoimmune renal disorder and prolongs survival; this may thus represent a novel approach to the treatment of patients with lupus nephritis.
Kinoshita
Koji
K
Division of Hematology, Nephrology, and Rheumatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. kinishita@int3.med.kindai.ac.jp
Yoo
Byun-Suk
BS
Nozaki
Yuji
Y
Sugiyama
Masafumi
M
Ikoma
Shinya
S
Ohno
Motoki
M
Funauchi
Masanori
M
Kanamaru
Akihisa
A
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000150:complications / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000209:etiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013163:Splenomegaly / Q000209:etiology / Q000517:prevention & control; D015996:Survival Rate; D014212:Tretinoin / Q000009:adverse effects / Q000627:therapeutic use*
D000974:Antibodies, Antinuclear; D016207:Cytokines; D007136:Immunoglobulins; D012333:RNA, Messenger; D014212:Tretinoin