Skip to main content
Log in

Effects of protein depletion on NK cell cytotoxicity and bone marrow cellularity

  • Nutritional Disturbances in Cancer Patients
  • Published:
Medical Oncology and Tumor Pharmacotherapy Aims and scope Submit manuscript

Abstract

Tumor bearing patients have repeatedly been shown to develop states of protein depletion (PD). PD has frequently been associated with depression of acquired immunity. In contrast, little is known about the effects of PD on natural killer (NK) cell cytotoxicity and on bone marrow cellularity and how modulation of these parameters by maleic anhydride divinyl ether copolymer (MVE-2) would be affected.

BALB/c mice 6–10 weeks old were fed normal diets (18% protein) (ND mice) or protein deficient isocaloric diets (PD mice) for 35 days. On days 5, 9, 15, 23, and 35 assays were performed. Three days prior to each assay day, some groups received MVE-2 i.p. In PD mice spontaneous NK activity was reduced by some 80%. After MVE-2 the levels only rose to half the amount of activity of ND mice, although in both groups an increase of NK activity took place. BMC levels of PD mice were also strongly decreased. After MVE-2, increases of BMC in PD mice were quite weak and did not reach the level of normal unstimulated BMC. In PD mice we found body weight loss of 46%, reduction in albumin and total protein of 22% and complete disappearance of prealbumin after 5 days of diets. Preliminary results indicate that repletion with amino acids (NeoAminomel L12.5 o.K.H. Salvia, Boehringer Mannheim Co.) is able restore NK activities and BMC levels.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chandra R K:Nutrition, Immunity and Infection (Mechanisms of Interactions), New York, Plenum Press (1977).

    Google Scholar 

  2. Smythe P M, Breton-Stiles G G, Grace H J, Mafoyane A, Schonland M, Coovadia H M, Loaning W E K, Parent M A, Vos G H: Thymolymphatic deficiency and depression of cell-mediated immunity in protein-calorie malnutrition.Lancet 2, 939 (1971).

    Article  PubMed  CAS  Google Scholar 

  3. Chandra R K: Nutritional modulation of immune response, in Kelley V C (ed):Practice of Pediatrics, New York, Harper & Row (1977).

    Google Scholar 

  4. Faulk W P: Effects of malnutrition on the immune response in humans: a review.Trop Dis Bull 72, 89 (1975).

    PubMed  CAS  Google Scholar 

  5. Fernandes G, Madhavan N, Kazunori O, Toshio T, Floyd R, Good R A: Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice.Proc Natl Acad Sci U.S.A. 76, 457 (1979).

    Article  PubMed  CAS  Google Scholar 

  6. Fernandes G, West A, Good R A: Nutrition, immunity and cancer—a review.Clin Bull 9, 91 (1979).

    PubMed  CAS  Google Scholar 

  7. Geefhuysen J, Rosen E U, Katz J, Ipp T, Metz J: Impaired cellular immunity in kwashiorkor with improvement after therapy.Br Med J 4, 257 (1971).

    Google Scholar 

  8. Gross R L, Newberne P M: Role of nutrition in immunologic function.Physiol Rev 60, 188 (1980).

    PubMed  CAS  Google Scholar 

  9. Grace H J, Armstrong D, Smythe P M: Reduced lymphocyte transformation in protein-calorie malnutrition.S Afr Med J 46, 402 (1972).

    PubMed  CAS  Google Scholar 

  10. Kulapongs P, Suskind R M, Vithayassi V, Olson R E:In vitro cell-mediated immune response in Thai children with protein-calorie malnutrition, in Suskind S S (ed):Malnutrition and the Immune Response, p. 99. New York, Raven Press (1977).

    Google Scholar 

  11. Kulapongs P, Edelman R, Suskind R, Olson R E: Defective local leukocyte mobilization in children with kwashiorkor.Am J Clin Nutr 30, 367 (1977).

    PubMed  CAS  Google Scholar 

  12. Alexander J W, Dionig R, Meakins J L: Periodic variation in antibacterial function of human neutrophils and its relationship to sepsis.Ann Surg 173, 206 (1971).

    PubMed  CAS  Google Scholar 

  13. Alexander J W, Hegg M, Altemeier W A: Neutrophil function in selected surgical disorders.Ann Surg 168, 447 (1968).

    Article  PubMed  CAS  Google Scholar 

  14. Beisel W R: Interrelated changes in host metabolism during generalized infectious illness.Am J Clin Nutr 25, 1254 (1972).

    PubMed  CAS  Google Scholar 

  15. Beisel W R: Metabolic response to infection.Ann Rev Med 26, 9 (1975).

    Article  PubMed  CAS  Google Scholar 

  16. Bell R G, Turner K J, Gracey M, Suharajano S: Serum and small intestinal immunoglobulin levels in undernourished children.Am J Clin Nutr 29, 392 (1976).

    PubMed  CAS  Google Scholar 

  17. Hanson L A, Brandtzaeg P: Secretory antibody systems, in Stiehm E R, Fulginiti V A (eds):Immunologic Disorders in Infants and Children, p. 107. Philadelphia, Saunders (1973).

    Google Scholar 

  18. Seth V, Chandra R K: Opsonic activity, phagocytosis and intracellular bactericidal capacity of polymorphs in undernutrition.Arch Dis Child 47, 282 (1972).

    Article  PubMed  CAS  Google Scholar 

  19. Daly J M, Dudrick S J, Copeland E M: Effects of protein depletion and repletion in cell mediated immunity in experimental animals.Ann Surg 188, 791 (1978).

    Article  PubMed  CAS  Google Scholar 

  20. Hamm M W, Winick M: Effect of protein restriction on macrophage phagocytic capacity in young mice.J Nutr 114, 511 (1984).

    PubMed  CAS  Google Scholar 

  21. Saxena Q B, Saxena R K, Adler W H: Effect of protein calorie malnutrition on the levels of natural and inducible cytotoxic activities in mouse spleen cells.Immunology 51, 727 (1984).

    PubMed  CAS  Google Scholar 

  22. Wing E J, Barcynski L K, Boehmer S M: Effect of acute nutritional deprivation on immune function in mice.Immunology 48, 543 (1983).

    PubMed  CAS  Google Scholar 

  23. Hersh E M, Chirigos M A, Mastrangelo M J,Augmenting Agents in Cancer Therapy, pp. 1–574. New York, Raven Press (1981).

    Google Scholar 

  24. Chirigos M A, Mitchell M, Mastrangelo M J, Krim M:Mediation of Cellular Immunity in Cancer by Immune Modifiers, pp. 1–269. New York, Raven Press (1981).

    Google Scholar 

  25. Herberman R B: Natural killer cell and other effector cells, and their roles in resistance against cncer, in Herberman R B, Friedman H (eds):The Reticuloendothelial System, vol. 5. New York, Plenum Press (1983).

    Google Scholar 

  26. Herberman R B:NK Cells and other Natural Effector Cells. New York, Academic Press (1982).

    Google Scholar 

  27. Herberman R B: Multiple functions of natural killer cells, including immunoregulation as well as resistance to tumor growth.Concepts Immunopath 1, 96 (1985).

    CAS  Google Scholar 

  28. Herberman R B: Biological response modifiers for the therapy of cancer.Rationale of Biological Response Modifiers in Cancer Treatment, 6th Hakone Symposium (1985).

  29. Talmadge J E, Maluish A E, Collins M, Schneider M, Herberman R B, Oldham R K, Wiltrout R H: Immunomodulation and antitumor effects of MVE-2 in mice.J Biol Resp Modif 3, 634 (1984).

    CAS  Google Scholar 

  30. Piccoli M, Saito T, Chirigos M A: Bimodal effects of MVE-2 on cytotoxic activity of natural killer cell and macrophage tumoricidal activities.Int J Immunopharmac 6, 569 (1984).

    Article  CAS  Google Scholar 

  31. Herberman R B, Nunn M E, Lavrin D H: Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution, reactivity and specificity.Int J Cancer 16, 216 (1975).

    Article  PubMed  CAS  Google Scholar 

  32. Schlick E. Friedberg K D: Bone marrow cells of mice under the influence of low lead doses.Arch Toxicol 49, 227 (1982).

    Article  PubMed  CAS  Google Scholar 

  33. Sigma Tech Bulletin No. 630 (9–80) 1980 (revised, 1983).

  34. BioRad Protein Assay Instruction Manual. BioRad Laboratories (1981).

  35. Anderson L, Anderson N G: High resolution twodimensional electrophoresis of human plasma proteins.Proc Natn Acad Sci U.S.A. 74, 5421 (1977).

    Article  CAS  Google Scholar 

  36. Bistrian B R, Blackburn G L, Hallowell E, Heddle R: Protein status of general surgical patients.J Am Med Assoc 230, 858 (1974).

    Article  CAS  Google Scholar 

  37. Bistrian B R, Blackburn G L, Vitale J, Cochran D, Naylor J: Prevalence of malnutrition in general medical patients.J Am Med Assoc 235, 1567 (1976).

    Article  CAS  Google Scholar 

  38. Ingenbleek Y, Visscher M, De Nayer: Measurement of prealbumin as index of protein-calorie malnutrition.Lancet 2, 106 (1972).

    Article  PubMed  CAS  Google Scholar 

  39. Blackburn G L, Schlamm H T: Nutritional assessment and treatment of hospital malnutrition, in van Eys J, Seeling M S, Nichols B L (eds):Nutrition and Cancer, pp. 1–30. New York, SP Medical and Scientific Books (1979).

    Google Scholar 

  40. Rosenberg E B, Herberman R B, Levine P H, Halterman R H, McCoy J L, Wunderlich J R: Lymphocyte cytotoxicity reactions to leukemiaassociated antigens in identical twins.Int J Cancer 2, 648 (1972).

    Article  Google Scholar 

  41. Roder J, Duwe A: The beige mutation in the mouse selectively impairs natural killer cell function.Nature 278, 451 (1979).

    Article  PubMed  CAS  Google Scholar 

  42. Talmadge T E, Meyers K M, Prieur D J, Starkey J R: Role of NK cells in tumor growth and metastasis in beige mice.Nature 284, 622 (1980).

    Article  PubMed  CAS  Google Scholar 

  43. Kärre K, Klein G O, Kiessling R, Klein G, Roder J C: Low naturalin vivo resistance to syngeneic leukaemias in natural killer-deficient mice.Nature 284, 624 (1980).

    Article  PubMed  Google Scholar 

  44. Barlozzari T, Reynolds C W, Herberman R B:In vivo role of natural killer cells: involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GM1-treated rats.J Immun 131, 1024 (1983).

    PubMed  CAS  Google Scholar 

  45. Miller S C: Production and renewal of murine natural killer cells in the spleen and bone marrow.J Immun 129, 2282 (1982).

    PubMed  CAS  Google Scholar 

  46. Haller O, Wigzell H: Suppression of natural killer activity with radioactive strontium: effector cells are bone marrow dependent.J Immun 118, 1503 (1977).

    PubMed  CAS  Google Scholar 

  47. Seaman W E, Blackman M A, Gindhart T D, Roubinian J R, Loeb J M, Talal N: Estradiol reduces natural killer cells in mice.J Immun 121, 2193 (1978).

    PubMed  CAS  Google Scholar 

  48. Haller O A, Gidlund M, Kurnick J T, Wigzell H:In vivo generation of mouse natural killer cells: role of the spleen and thymus.Scand J Immun 8, 207 (1978).

    Article  CAS  Google Scholar 

  49. Trentin J J, Kiessling R, Wigzell H, Gallagher M T, Datta S K, Kulkarni S S: Bone marrow transplantation immunobiology, in Baum S J, Ledney G D (eds):Experimental Hematology Today, p. 181, New York, Springer (1977).

    Google Scholar 

  50. Schlick E, Ruffmann R, Chirigos M A, Welker R D, Herberman R B:In vivo modulation of myelopoiesis and immune functions by MVE-2 in tumor-free and MBL-2 tumor-bearing mice treated with cyclophosphamide.Cancer Res 45, 1108 (1985).

    PubMed  CAS  Google Scholar 

  51. Chirigos M A, Saito T, Schlick E, Ruffmann R: Cellular regulation by immunomodifiers MVE-2 and Poly ICLC and their therapeutic application.Cancer Treat Symp, vol. 1 (1985).

  52. Gorelik E, Herberman R B: Inhibition of the activity of mouse NK cells by urethane.J Natn Cancer Inst 66, (1981).

  53. Gorelik E, Rosen B, and Herberman R B: Depression of NK reactivity in mice by leukemogenic doses of irradiation, in Herberman R B (ed):NK Cells and other Natural Effector Cells, pp. 1423–1430. New York, Academic Press (1982).

    Google Scholar 

  54. Parkinson D R, Brightman R P, Waksal S D: Altered natural killer cell biology in C57BL/6 mice after leukemogenic split-dose inoculation.J Immun 126, 1460 (1981).

    PubMed  CAS  Google Scholar 

  55. Blackburn G L, Bistrian B R: Careers in nutrition from the clinical viewpoint.Nutr Rev 34, 97 (1976).

    Article  PubMed  CAS  Google Scholar 

  56. Harvey K B, Bothe A, Jr, Blackburn G L: Nutritional assessment and patient outcome during oncological therapy.Cancer 43, 2065 (1979).

    Article  PubMed  CAS  Google Scholar 

  57. Van Eys J: Malnutrition in children with cancer: incidence and consequence.Cancer 43, 2030 (1979).

    Article  PubMed  Google Scholar 

  58. De Wys W D: Nutritional care of the cancer patient.J Am Med Assoc 244, 374 (1980).

    Article  Google Scholar 

  59. Donaldson S S, Lenon R A: Alterations of nutritional status: impact of chemotherapy and radiation therapy.Cancer 43, 2036 (1979).

    Article  PubMed  CAS  Google Scholar 

  60. Van Eys J: Nutrition and neoplasia.Nutr Rev 40, 353 (1982).

    PubMed  Google Scholar 

  61. Fabris C, Piccoli A, Meani A, Farini R, Vianello D, Del Favero G, Sturniolo G, Brosolo P, and Naccarato R: Study of retinol-binding protein in pancreatic cancer.J Cancer Res Clin Oncol 108, 227 (1984).

    Article  PubMed  CAS  Google Scholar 

  62. Copeland E M, Rodman C A, Dudrick S J: Nutritional concepts of neoplastic disease, in Van Eys J, Seeling M S, Nichols B L (eds):Nutrition and Cancer, pp. 133–156. New York, SP Medical and Scientific Books (1979).

    Google Scholar 

  63. Bistrian B R, Blackburn G L, Scrimshaw N S, Flatt J P: Cellular immunity in semistarved states in hospitalized adults.Am J Clin Nutr 28, 1148 (1975).

    PubMed  CAS  Google Scholar 

  64. Bistrian B R, Sherman M, Blackburn G L, Marshall R, Shaw, C: Cellular immunity in adult marasmus.Arch Intern Med 137, 1408 (1977).

    Article  PubMed  CAS  Google Scholar 

  65. Shils M E: Nutritional problems associated with gastrointestinal and genitourinary cancer.Cancer Res 37, 2366 (1977).

    PubMed  CAS  Google Scholar 

  66. Brennan M F: Uncomplicated starvation versus cancer cachexia.Cancer Res 37, 2359 (1977).

    PubMed  CAS  Google Scholar 

  67. Copeland E M III, Daly J M, Dudrick S J: Nutrition as an adjunct to cancer treatment in the adult.Cancer Res 37, 2451 (1977).

    PubMed  Google Scholar 

  68. Ruffman R, Tartaris T, Schlick E, Welker R D, Saito T, Gregorio T, Chirigos M A: Auswirkungen des proteinmangels auf die natuerliche immunitaet, in Striebel J P, Hennigsen B, Kluther R (eds):Klinische Ernaehrung Im Gespraech, pp. 102–111, Muenchen, Zuckschwerdt (1985).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruffmann, R., Schlich, E., Tartaris, T. et al. Effects of protein depletion on NK cell cytotoxicity and bone marrow cellularity. Med. Oncol. & Tumor Pharmacother. 2, 195–202 (1985). https://doi.org/10.1007/BF02934548

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02934548

Key words

Navigation