Predominant inhibition of Th1 cytokines in New Zealand black/white F1 mice treated with FK506.
The T-helper 1/T-helper 2 (Th1/Th2) cell balance was examined in 6-month-old New Zealand black/white F1 (B/WF1) mice treated with an immunosuppressive agent, FK506. The survival rate of mice treated with 10 mg/kg/day of FK506 was 7/8, while that of those treated with 2.5 mg/kg/day was 5/8, and 4/8 after treatment for 8 weeks with placebo. Proteinuria, which was already positive in all mice before the treatment, in the seven of eight mice treated with 10 mg/kg/day remained mildly positive (< or = 1+), while seven of eight mice treated with 2.5 mg/kg/day and six of eight mice treated with the placebo showed severe proteinuria (> or = 2+). Pathological changes in the kidneys of mice treated with 10 mg/kg/day of FK506 were less severe than in mice treated with the placebo or 2.5 mg/kg/day of FK506. Expression of mRNA was unchanged for all cytokines determined in the groups treated with 2.5 mg/kg/day of FK506 or placebo. In contrast, expression of mRNA for interleukin (IL)-2, and interferon (IFN)-gamma was suppressed, while that for IL-4 and IL-10 was not suppressed in the group treated with 10 mg/kg of FK506. The serum levels of IgG-class anti-DNA antibodies, which had been elevated before the treatment, were suppressed--especially in the IgG2a subclass--and the deposition of IgG2a and IgG2b in the glomeruli was reduced in the group treated with 10 mg/kg/day of FK506 compared with the other groups. These findings suggest that an improvement in the lupus nephritis of 6-month-old B/WF1 mice induced by FK506 might be associated with a predominant inhibition of Th1 cytokine.
Sugiyama
M
M
Division of Haematology, Nephrology, and Rheumatology, Kinki University School of Medicine, Osaka, Japan. sugiyama@nara.med.kindai.ac.jp
Funauchi
M
M
Yamagata
T
T
Nozaki
Y
Y
Yoo
B S
BS
Ikoma
S
S
Kinoshita
K
K
Kanamaru
A
A
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000187:drug effects; D001483:Base Sequence; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D011336:Probability; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016559:Tacrolimus / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
D000974:Antibodies, Antinuclear; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016559:Tacrolimus