The purpose of this study was to determine whether arginine supplementation enhances in vitro (neutrophil burst and mitogen-induced lymphocyte proliferation) and in vivo (delayed-type hypersensitivity [DTH] and serum nitric oxide) measures of immune function in nursing home elders with pressure ulcers. Twenty-six elders, 65 years of age or older, with one or more pressure ulcers, were randomized to receive 8.5 g of arginine or an isonitrogenous supplement for 4 weeks. Immune function studies and serum arginine, ornithine, citrulline, and nitric oxide were measured at baseline, 4 weeks postsupplementation (Week 4) and after a 6-week washout (Week 10). At Week 4, serum ornithine increased (p = .01) and arginine trended to increase (p = .055), but there was no increase in citrulline or nitric oxide with arginine supplementation. There were no differences in neutrophil burst or DTH responses between groups. Whole blood mitogen–induced proliferation decreased significantly atWeek 10 in the isonitrogenous but not in the arginine-supplemented group. There is mounting concern that arginine supplementation during an inflammatory state could be detrimental due to overwhelming nitric oxide production. A key finding of this study is that arginine supplementation did not increase serum nitric oxide levels over that observed in elders with pressure ulcers given an isonitrogenous supplement.
Albina, J. E., Mills, C. C., Henry, W. L.,& Caldwell, M. D. (1990). Temporal expression of different pathways of l-arginine metabolism in healing wounds. Journal of Immunology, 144(10), 3877-3880.
2.
Ashcroft, G. S., Dodsworth, J., van Boxtel, E., Tarnuzzer, R. W., Horan, M. A., Schultz, G. S., et al. (1997). Estrogen accelerates cutaneous wound healing associated with an increase in TGFbeta1 levels. Nature Medicine, 3(11), 1209-1209, 1215-1215.
3.
Barbul, A., Fishel, R. S., Shimazu, S., Wasserkrug, H. L., Yoshimura, N. N., Tao, R. C., et al. (1985). Intravenous hyperalimentation with high arginine levels improves wound healing and immune function. Journal of Surgical Research, 38, 331-337.
4.
Barbul, A., Lazarou, S. A., Efron, D. T., Wasserkrug, H. L., & Efron, G. (1990). Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery, 108, 331-337.
5.
Barbul, A., Sisto, D. A., Wasserkrug, H. L., & Efron, G. (1981). Arginine stimulates lymphocyte immune response in healthy human beings. Surgery, 90, 244-250.
6.
Berkowitz, D. E., White, R., Li, D., Minhas, K. M., Cernetich, A., Kim, S., et al. (2003). Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation, 108, 2000-2006.
7.
Bode-Boger, S. M., Boger, R. H., Galland, A., Tsikas, D., & Frolich, J. C. (1998). L-arginine-induced vasodilation in healthy humans: Pharmacokinetic-pharmacodynamic relationship. British Journal of Clinical Pharmacology, 46, 489-497.
8.
Bonnefoy, M., Coulon, L., Bienvenu, J., Boisson, R. C., & Rys, L. (1995). Implication of cytokines in the aggravation of malnutrition and hypercatabolism in elderly patients with severe pressure sores. Age and Ageing, 24, 37-42.
9.
Childress, B., & Stechmiller, J. (2002). Role of nitric oxide in wound healing. Biological Research for Nursing, 4, 5-15.
10.
Corberand, J., Ngyen, F., Laharrague, P., Fontanilles, A. M., Gleyzes, B., Gyard, E., et al. (1981). Polymorphonuclear functions and aging in humans. Journal of the American Geriatric Society, 29, 41-45.
11.
Daly, J. M., Lieberman, M. D., Goldfine, J., Shou, J., Weintraub, F., Rosato, E. F., et al. (1992). Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operational: Immunologic, metabolic, and clinical outcome. Surgery, 112, 56-67.
12.
Flynn, N. E., & Wu, G. (1997). Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs. Journal of Nutrition, 127, 732-737.
13.
Hudgens, J., Langkamp-Henken, B., Stechmiller, J. K., Herrlinger-Garcia, K. A., & Nieves, C, Jr. (In press). Immune function is impaired with a Mini Nutritional Assessment score indicative of malnutrition in nursing home elders with pressure ulcers. JPEN. Journal of Parenteral and Enteral Nutrition.
14.
Hurson, M., Regan, M. C., Kirk, S. J., Wasserkrug, H. L.,& Barbul, A. (1995). Metabolic effects of arginine in a healthy elderly population. JPEN. Journal of Parenteral and Enteral Nutrition, 19, 227-230.
15.
Kirk, S. J., Hurson, M., Regan, M. C., Holt, D. R., Wasserkrug, H. L.,& Barbul, A. (1993). Arginine stimulateswoundhealing and immune function in elderly human beings. Surgery, 114, 155-160.
16.
Kissin, E., Tomasi, M., McCartney-Francis, N., Gibbs, C. L., & Smith, P. D. (1997). Age-related decline in murine macrophage production of nitric oxide. Journal of Infectious Disease, 175, 1004-1007.
17.
Knicker, W. T., Anderson, C. T., McBryde, J. L., Roumiantzeff, M., & Lesourd, B. (1984). Multitest CMI for standardized measurement of delayed cutaneous hypersensitivity and cellmediated immunity. Normal values and proposed scoring system for healthy adults in the U.S.A. Annals of Allergy, 52, 75-82.
18.
Langkamp-Henken, B., Herrlinger-Garcia, K., Stechmiller, J. K., Nickerson, J., Lewis, B., & Moffatt, L. (2000). Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers. JPEN. Journal of Parenteral and Enteral Nutrition, 5, 280-286.
19.
Langkamp-Henken, B., Johnson, L. R., Viar, M. J., Geller, A. M., & Kotb, M. (1998). Differential effect on polyamine metabolism in mitogen-and superantigen-activated human t-cells. Biochimica et Biophysica Acta, 1425, 337-347.
20.
Leigh, I. H.,& Bennett, G. (1994). Pressure ulcers: Prevalence, etiology and treatment modalities. American Journal of Surgery, 167(1A), 25S-30S.
21.
Lesourd, B. (1995). Protein undernutrition as the major cause of decreased immune function in the elderly: Clinical and functional implications. Nutrition Reviews, 53(4), S86-S94.
22.
Lyder, C. H. (2003). Pressure ulcer prevention and management. Journal of the American Medical Association, 289, 223-226.
23.
Mackinodan, T., & Kay, M. M. B. (1980). Age influence on the immune system (Review). Advanced Immunology, 29, 287-330.
24.
Macphail, S. E., Gibney, C. A., Brooks, B. M., Booth, C. G., Flanagan, B. F., & Coleman, J. W. (2003). Nitric oxide regulation of human peripheral blood mononuclear cells: Critical time dependence and selectivity for cytokine versus chemokine expression. Journal of Immunology, 171, 4809-4815.
25.
Marik, P.E., & Saloga, G.P. (2001). Early enteral nutrition in acutely ill patients: A systematic review. Critical Care Medicine, 12,2264-2270.
26.
Mathus-Vliegen, E. (2004). Old age, malnutrition, and pressure sores. Journal of Gerontology, 59A, 355-360.
27.
Moinard, C., Caldefie-Chezet, F., Walrand, S., Vasson, M. P., & Cynober L. (2002). Evidence that glutamine modulates respiratory burst in stressed rat polymorphonuclear cells through its metabolism into arginine. British Journal of Nutrition, 88, 689-695.
28.
Murasko, D. M., Weiner, P.,& Kaye, D. (1987). Decline in mitogen induced proliferation of lymphocytes with increasing age. Clinical and Experimental Immunology, 70, 440-448.
29.
Nieves, C., & Langkamp-Henken, B. (2002). Arginine and immunity: A unique perspect ive. Biomedicine and Pharmacotherapy, 56, 471-482.
30.
Nirgiotis, J., Hennessey, P., & Andrassy, R. (1991). The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. Journal of Pediatric Surgery, 26, 936-941.
31.
Perier, C., Granouillet, R., Chamson, A., Gonthier, R., & Frey, J. (2002). Nutritional markers, acute phase reactants and tissue inhibitor of matrix metalloproteinase 1 in elderly patients with pressure sores. Gerontology, 48, 298-301.
32.
Preiser, J. C., Berre, P. J., Van Gossum, A., Cynober, L., Vray, B., Carpentier, Y., et al. (2001). Metabolic effects of arginine addition-to the enteral feeding of critically ill patients. JPEN. Journal-of Parenteral and Enteral Nutrition, 25, 182-187.
33.
Rizk, M., Witte, M., & Barbul, A. (2004). Nitric oxide and wound healing. World Journal of Surgery, 28, 301-206.
34.
Simpson, D. M., & Ross, R. (1972). The neutrophilic leukocyte in wound repair. A study with antineutrophil serum. Journal of Clinical Investments, 51, 2009-2023.
35.
Sitren, H., & Fisher, H. (1977). Nitrogen retention in rats fed on diets enriched with arginine and glycine. 1. Improve N retention after trauma. British Journal of Nutrition, 37, 195-208.
36.
Stechmiller, J., & Langkamp-Henken, B. (2003, February). Arginine & immune status in elderly with pressure ulcers[Abstract]. Proceedings of the 17th Annual Conference of the Southern Nursing Research Society, Orlando, FL.
37.
Stechmiller, J. K., Langkamp-Henken, B., & Childress, B. (2002, February). Biochemical analysis of wound fluid from chronic wounds of older hospitalized patients[Abstract]. Proceedings of the 16th Annual Conference of the Southern Nursing Research Society, San Antonio, TX.
38.
Stechmiller, J. K., Paddock, H. N., Gowda, A., Mozingo, D., Chinn, G., Porter, T., et al. (2002). Biochemical analysis of wound fluid from chronicwounds treated withVAC[Abstract]. Wound Repair and Regeneration, 10(2), A54-A54.
39.
Suchner, U., Heyland, D. K., & Peter, K. (2002). Immunemodulatory actions of arginine in the critically ill. British Journal of Nutrition, 87(Suppl. 1), S121-S132.
40.
Suschek, C. V., Schnorr, O., Hemmrich, K., Aust, O., Klotz, L. O., Sies, H., et al. (2003). Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation, 107, 2607-2614.
41.
Tangphao, O., Chalon, S., Coulston, A. M., Moreno, H., Jr., Chan, J. R., Cooke, J. P., et al. (1999). L-arginine and nitric oxiderelated compounds in plasma: Comparison of normal and arginine-free diets in a 24-h crossover study. Vascular Medicine, 4, 27-32.
42.
Thomas, D. R. (1996). Hospital acquired pressure ulcers and risk of death. Journal of the American Geriatrics Society, 44(12), 1435-1435.
43.
Witte, M.,& Barbul, A. (2003). Arginine physiology and its implications for wound healing. Wound Repair and Regeneration, 11, 419-423.
44.
Witte, M. B., & Barbul, A. (2002). Role of nitric oxide in wound repair. American Journal of Surgery, 183, 406-412.
45.
Wysocki, A. B. (1999). Decubitus ulcers. In I. M. Freedberg, A. Z. Eisen, K. Wolff, K. F. Austen, L. A. Goldsmith, S. I. Katz, et al. (Eds.), Dermatology in general medicine(pp. 1538-1554). New York: McGraw-Hill.
46.
Yarkony, G. M. (1993). Aging skin, pressure ulcerations and spinal cord injury. In G. G. Whiteneck (Ed.), Aging with spinal cord(pp. 39-52). New York: Demos.
47.
Yarkony, G. M. (1994). Pressure ulcers: A review. Archives of Physical Medicine and Rehabilitation, 75, 908-917.
