Effect of mizoribine on IL-6 release by peripheral blood mononuclear cells.
OBJECTIVE
A novel immunosuppressant, mizoribine (MZB), has recently been reported to be effective in the treatment of IgA nephropathy (IgAN), although its mechanism of action remains unknown. This study was conducted to investigate whether the efficacy of MZB on IgAN is exerted by suppression of interleukin-6 (IL-6) release.


METHODS
Peripheral blood mononuclear cells (PBMC) were collected from 4 children with IgAN (median age 13.0 years) and 4 control children (median age 5.2 years). PBMC were cultured with medium alone or medium with lipopolysaccharide (LPS), and then incubated with LPS and MZB. Culture supernatants were assayed for lL-6.


RESULTS
IL-6 release was increased by LPS in all subjects. Although the median value was higher in IgAN patients (median increase in IL-6 release 1,298.1%) than in controls (median 489.2%), statistical significance was not reached (p > 0.05). 10 mg/ml of MZB suppressed the release of IL-6 in both IgAN patients (median decrease in IL-6 release 39.3%) and controls (median 43.2%), with statistical significance (p < 0.05 and p < 0.01, respectively).


CONCLUSIONS
This study suggests that MZB could suppress IL-6 release in vitro and thus may exert its efficacy on IgAN.
Department of Pediatrics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 Japan. kkaneko@med.juntendo.ac.jp
Kazunari
K
Kaneko
Rieko
R
Nagaoka
Yoshiyuki
Y
Ohtomo
Toshiaki
T
Shimizu
Yuichiro
Y
Yamashiro
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012263:Ribonucleosides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D015850:Interleukin-6; D012263:Ribonucleosides; C010052:mizoribine