The weak calcemic vitamin D3 analogue 22-oxacalcitriol suppresses the production of tumor necrosis factor-alpha by peripheral mononuclear cells.
The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue 22-oxacalcitriol (OCT), which was reported to have very weak bone resorbing activity, on the production of tumor necrosis factor (TNF)-alpha was investigated. Mononuclear cells (MNC; 10(6)/ml) were incubated in 5% FCS/RPMI-1640 medium containing 1 microgram/ml lipopolysaccharide (LPS) in the presence or absence of 10(-8) M 1,25(OH)2D3 or 10(-8) M OCT for up to 96 h. Both 1,25(OH)2D3 and OCT suppressed TNF-alpha release by LPS-stimulated mononuclear cells, from the early to late stage of the incubation period, while neither 1,25(OH)2D3 nor OCT shifted the peak time point of TNF-alpha release clearly. MNC (10(6)/ml) were incubated with 1 microgram of LPS in the presence of various concentrations of 1,25(OH)2D3 or 10(-8) M OCT for 48 h. 1,25(OH)2D3 reduced TNF-alpha levels of LPS-stimulated MNC culture supernatant at 48 h in a dose-dependent manner. The half-maximal dose (ED50) for this suppressive effect was 3.7 x 10(-9) M. OCT decreased TNF-alpha levels of culture supernatant at 48 h with a half-maximal dose of 7.8 x 10(-11) M, which indicates that it is approximately 50 times more potent than that of 1,25(OH)2D3. These results indicate that OCT may be applicable as an immunosuppressive agent with limited calcium metabolic activity.
Fujibayashi
S
S
Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Suzuki
S
S
Okano
K
K
Naitoh
T
T
Katabami
T
T
Someya
K
K
D000328:Adult; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002117:Calcitriol; C051883:maxacalcitol