Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

The in vivo effect of a new, in vitro, extremely potent vitamin D3 analog KH1060 on the suppression of renal allograft rejection in the rat


KH1060 is a new 20-epi-vitamin D3 analog, which has exerted a considerable immunosuppressive potency in vitro. We have tested in vivo the effect of KH1060 on the suppression of renal allograft rejection in the rat. Allogenic kidney transplantation from DA donor rats to Lewis recipient rats treated intraperitoneally with KH1060 in doses from 0.2 to 6 μg/kg/day, or saline (placebo group), or CyA 10 mg/kg/day for 10 days (positive control group), was performed. Median graft survival time in KH1060-treated groups was 7–9 days, in the placebo group 6 days, whereas CyA led to long-term graft survival, 34 days in 50% of rats and >100 days in 50% of rats. In vivo, KH1060 failed to prolong renal allograft survival considerably, and led to development of hypercalcemia. Our results stress the existence of a large discrepancy between the in vitro and in vivo immunoregulatory effects of this vitamin D analog.

This is a preview of subscription content, log in to check access.


  1. 1.

    Provvedini DM, Tsukas CD, Deftos LJ, Manolagas SC (1983) 1,25-Dihydroxyvitamin D3 receptors in human leucocytes. Science 221:1181–1182

  2. 2.

    Tsukas CD, Provvedini DM, Manolagas SC 1,25-Dihydroxy-vitamin D3 (1984). A novel immunoregulatory hormone. Science 224:1438–1439

  3. 3.

    Tsukas CD, Watry D, Escobar SS, Provvedini DM, Dinarello CA, Hustmyer FG, Manolagas SC (1989) Inhibition of interleukin-1 production by 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab 69:127–133

  4. 4.

    Rigby WFC, Denome S, Fanger MW (1987) Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. J Clin Invest 79:1659–1664

  5. 5.

    Muller K, Diamant M, Bendtzen K (1991) Inhibition of production of interleukin-6 by 1,25-dihydroxyvitamin D3. Immunol Lett 28:115–120

  6. 6.

    Brown AJ, Finch JL, Lopez-Hilker S, Dusso A, Ritter C, Pernalete N, Slatoposky E (1990) New active analogues of vitamin D with low calcemic activity. Kidney Int 38:S22-S27

  7. 7.

    Abe J, Takita Y, Nakano T, Miyaura C, Suda T, Nishii Y (1989) A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxyvitamin D3, is a potent modulator of in vivo immunoregulating activity withooutinducing hypercalcemia in mice. Endocrinology 124:2645–2647

  8. 8.

    Binderup L, Latini S, Binderup E, Bretting C, Calverley M, Hansen K (1991) 20-epi-vitamin D3 analogues: a novel class of potent regulators of cell growth and immune responses. Biochem Pharmacol 42:1569–1575

  9. 9.

    Lillevang ST, Rosenkvist J, Andersen CB, Larsen S, Kemp E, Kristensen T (1992) Single and combined effects of the vitamin D analogue KH1060 and cyclosporin A on mercuric-chloride-induced autoimmune disease in BN rat. Clin Exp Immunol 88: 301–306

  10. 10.

    Veyron P, Pamphile R, Binderup L, Touraine JL (1993) Two novel vitamin D analogues, KH1060 and CB 966, prolong skin allograft survival in mice. Transplant Immunol 1:72–76

  11. 11.

    Lewin E, Colstrup H, Pless V, Ladefoged J, Olgaard K (1993) A model of reversible uremia employing isogenic kidney transplantation in the rat. Scand J Urol Nephrol 27:115–120

  12. 12.

    Funder JW, Pearce PT, Smith R, Smith AI (1988) Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583–585

  13. 13.

    Dusso A, Negrea L, Lopez-Hilker S, Finch J, Mori T, Nishii Y, Slatopolsky E, Brown AJ (1991) Noncalcemic vitamin D analogs and mechanisms for their selectivity. 8. Workshop on vitamin D (abstracts) Paris, p 195

  14. 14.

    Tsugawa N, Okano T, Masuda S, Takeuchi A, Kobayashi T, Nishii Y (1989) Comparative study on the protein binding of a novel synthetic vitamin D3 analogue [22-oxa-1,25-dihydroxy-vitamin D3] and various vitamin D3 metabolites (abstract 418) J Bone Miner Res 4:S222

  15. 15.

    Slatopolsky E, Berkoben M, Kelber J, Brown A, Delmez J (1992) Effects of calcitriol and non-calcemic vitamin D analogs on secondary hyperparathyroidism. Kidney Int 42:S43-S49

  16. 16.

    Klinger M, Alexiewicz JM, Linker-Israeli M, Pitts TO, Gaciong Z, Fadda GZ, Massry SG (1990) Effect of parathyroid hormone on human T cell activation. Kidney Int 37:1543–1551

  17. 17.

    Lewin E, Ladefoged J, Brandi L, Olgaard K (1993) Parathyroid hormone-dependent T cell proliferation in uremic rats. Kidney Int 44:379–384

  18. 18.

    Perris AD, Weiss LA, Whitfield JF (1970) Parathyroidectomy and the induction of thymic atrophy in normal, adrenalectomized and orchidectomized rats. J Cell Physiol 76:141–150

  19. 19.

    Perris AD, Edwards DJ, Atkinson MJ (1984) Some effects of parathyroidectomy on cell-mediated immune responses in the rat. J Endocrinol 102:257–263

  20. 20.

    Rigby WFC, Hamilton BJN (1991) Regulation of T lymphocyte activation at a posttranscriptional level by 1,25-dihydroxyvitamin D3. 8. Workshop on vitamin D (abstract) Paris, p 196

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lewin, E., Olgaard, K. The in vivo effect of a new, in vitro, extremely potent vitamin D3 analog KH1060 on the suppression of renal allograft rejection in the rat. Calcif Tissue Int 54, 150–154 (1994).

Download citation

Key words

  • Vitamin D analog
  • KH1060
  • Kidney transplantation
  • Rat