Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지

Neutralizing Effects of Antiserum by Repeated Subcutaneous Administration of Recombinant Human Growth Hormone (rhGH)

  • Song, Yeon-Jung (Institute of Bioscience ＆ Biotechnology, Daewoong Pharmaceutical Co.) ;
  • Park, Shin-Hye (Institute of Bioscience ＆ Biotechnology, Daewoong Pharmaceutical Co.) ;
  • Park, Seung-Kook (Institute of Bioscience ＆ Biotechnology, Daewoong Pharmaceutical Co.) ;
  • Yeon, Je-Deuk (Institute of Bioscience ＆ Biotechnology, Daewoong Pharmaceutical Co.)
  • Published : 2002.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Human growth hormone (hGH) forms antibody by repeated administration. The present study investigated to confirm formation of antibody by repeated subcutaneous administration of hGH for two months in rats and dogs. In this result, hGH-injected sera were significantly higher than control sera by 1:1,000,000 of dilution factor. After antibody formed sera (anti-hGH sera) and control sera were added to 30 $\mu\textrm{g}$/ml hGR, the complex incubated for overnight at $30^{\circ}C$. Anti-hGH sera decreased hGH contents about 90% compared to control sera. Also, body weight gain conducted decreased about 67% compared to control sera in hypophysectomised rat. Inconclusion, repeated administration of hGH formed antibody because hGH was foreign protein to rats and dogs. And formed antibody of hGH was blocked and decreased many efficacy of hGH, the antibody was proved to be neutralizing antibody. Thus, because neutralizing antibodies were decreased pharmacological effects of hGH, administration more than two months were no significance.

Keywords

References

  1. Answer, L., Shi, M., French, M. F, Muller, S. R., Chen, W., Liu, Q., Proeor, B. L., Wang, J., Mumper, R. J., Singhal, A., Rolland, A. P. and Alila, H. W. (1998). Systemic effect of Human growth hormone after intramuscular injection of a sin- gle dose of a muscle-specific gene medicine, Hum. Gene. Ther, 9, 659-670 https://doi.org/10.1089/hum.1998.9.5-659
  2. Chawla, R. K., Parks, J. S. and Rudman, D. (1983). Structural variants of human growth hormone: biochemical, genetic, and clinical aspects, Annu. Rev. Med., 34, 519-547 https://doi.org/10.1146/annurev.me.34.020183.002511
  3. Council of Europe. (1987). Hormonum humanium incrementi ad injectable. European pharmacopeia, 556, Maisoinneuve S.A
  4. De Muinck Keizer-Schrams, S. and Rikken, B, (1992). Growth hormone deficiency: Groeihormoondeficientic: diagnostiek en behandeling, Tijdschrift voor kindergeneeskunde, 60, 147-154
  5. Dorchy, H., Duchateau, J., Bosson, D. and DHooge, D. (1989). Transfer from purified porcine insulins ro semisynthetic human insulins decreases insulin antibodies and circulating immune complex in diabetic children and adolescents. A two-year fol- low-up, Diabete Metab., 15, 107-110
  6. Duquesnoy, R. J. and Good, R. A. (1970). Growth inhibition of newborn rats by plasma of monkeys immunized against rat growth hormone, J. Endocr., 48, 465-466 https://doi.org/10.1677/joe.0.0480465
  7. Edwards, C. K., Ghiasuddin, S. M., Schepper, J. M. and Yunger, L. M. (1988). A Newly defined property of somatotropin: priming of macrophages for production of superoxide anion, Science, 239, 769-771 https://doi.org/10.1126/science.2829357
  8. Farrington, M. A. and Hymer, W. C. (1987). An enzyme Immu-noasay for rat growth hormone : Applications to the study of growth hormone variants, Life sciences, 40, 2479-2488 https://doi.org/10.1016/0024-3205(87)90068-3
  9. Flint, D. J. and Gardner, M. J. (1989). Inhibition of neonatal rat growth and circulating concentrations of insulin-like growth factor I using an antiserum to rat growth hormone, J. endo- crinol., 122, 79-86
  10. Fraisier, S. D. (1983). Human pituitary growth hormone (hGH) therapy in growth hormone deficiency, Endocr. Rev., 4, 155- 170 https://doi.org/10.1210/edrv-4-2-155
  11. Gause, I., Eden, S., Janssen, J. 0. and Isaksson, 0. (1983). Effects of in vivo administration of antiserum to rat growth hormone on body growth and insulin responsiveness in adipose tissue, Endocrinology, 112, 1559-1566 https://doi.org/10.1210/endo-112-5-1559
  12. Hayashida, T. and Contopoulas, A. N. (1967). Immunological studies with rat pituitary growth hormone. I. Basic studies with immunodiffusion and antihormone tests, Gen. Comp. Endo- crinol., 9, 217-226 https://doi.org/10.1016/0016-6480(67)90055-X
  13. Henrik Agerso, D., Michael Wliken, M. Jorn Drustrup, M., Poul- Martin, H. and Karin Damm, J. (1999). Plasma concentration of hGH and anti-hGH antibodies after subcutaneous adminis- tration of hGH for 3 weeks to immunosupressed pigs, J. Phar- macol. Toxicol., 41, 1-8 https://doi.org/10.1016/S1056-8719(99)00017-9
  14. Makower, A. M., Wroblewski, J. and Pawlowski, A. (1989). Effects of IGF-I, rGH, EGF and NCS o DNA synthesis, cell proloferation and morphology of chondrocytes isolated from rat rib growth cartilage. Cell Biol Int. Rep., 13, 259-270 https://doi.org/10.1016/0309-1651(89)90148-3
  15. Mulls, P. E. and Brickell, P. M. (1992). The use of polymerase chain reaction in prenatal diagnosis of growth hormone gene deletion. Clinical. Endocrinology, 37, 89-95 https://doi.org/10.1111/j.1365-2265.1992.tb02288.x
  16. Palmer, R. M., Loveridge, N., Tomson, B. M., Mackie, S. C., Tonner, E. and Flint, D. J. (1994). Effects of a polyclonal anti- serum to rat growth hormone on circulationg IGF-I and IGF-I binding protein concentrations and the growth of muscle and bone. J. Endoctinol, 142, 85-91 https://doi.org/10.1677/joe.0.1420085
  17. Rehlaender, B. N. and Cho, M. J. (1998). Antibodies as carrier Proteins, Pharm Res, 1652-1656
  18. Schlemmer, A., Johansen, J. S., Pederden, S. A., Jorgenson, J. 0., Hassager, C. and Christiansen, C. (1991). The effect of growth hormone (GH) therapy on urinary pyridinoline cross-links in GH deficient adults, Clin- Endocrinol., 35, 471-476 https://doi.org/10.1111/j.1365-2265.1991.tb00930.x
  19. Schurmann, A., Spencer, G. S. G. and Berry, C. J. (1995). Growth hormone alters lymphocyte sub-populations and antibody pro- duction in dwarf rats in vivo, Experientia, 51, 780-785 https://doi.org/10.1007/BF01922430