The DOI matches its Crossref record; 250 of the 250 references it cites were found in a registry or an index.
Zinc and immune function: the biological basis of altered resistance to infection
Open accessAbstract
Zinc is known to play a central role in the immune system, and zinc-deficient persons experience increased susceptibility to a variety of pathogens. The immunologic mechanisms whereby zinc modulates increased susceptibility to infection have been studied for several decades. It is clear that zinc affects multiple aspects of the immune system, from the barrier of the skin to gene regulation within lymphocytes. Zinc is crucial for normal development and function of cells mediating nonspecific immunity such as neutrophils and natural killer cells. Zinc deficiency also affects development of acquired immunity by preventing both the outgrowth and certain functions of T lymphocytes such as activation, Th1 cytokine production, and B lymphocyte help. Likewise, B lymphocyte development and antibody production, particularly immunoglobulin G, is compromised. The macrophage, a pivotal cell in many immunologic functions, is adversely affected by zinc deficiency, which can dysregulate intracellular killing, cytokine production, and phagocytosis. The effects of zinc on these key immunologic mediators is rooted in the myriad roles for zinc in basic cellular functions such as DNA replication, RNA transcription, cell division, and cell activation. Apoptosis is potentiated by zinc deficiency. Zinc also functions as an antioxidant and can stabilize membranes. This review explores these aspects of zinc biology of the immune system and attempts to provide a biological basis for the altered host resistance to infections observed during zinc deficiency and supplementation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Both human and animal studies have shown a correlation between zinc deficiency and enhanced susceptibility to infection.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [190]
In the citing paper
“Many animal studies show that zinc deficiency decreases resistance to a range of bacterial, viral, fungal, and parasitic pathogens (29), probably because of the immune impairment induced by zinc deficiency.”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [29]
In the citing paper
“Many animal studies show that zinc deficiency decreases resistance to a range of bacterial, viral, fungal, and parasitic pathogens (29), probably because of the immune impairment induced by zinc deficiency.”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [29]
In the citing paper
“Zinc supplementation decreased not only the production of inflammatory cytokines but also that of oxidative stress markers, as we previously reported (19,29).”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [29]
In the citing paper
“Numerous studies have shown the benefits of zinc supplementation with respect to infectious diseases in human populations (29).”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [29]
In the citing paper
“Zinc supplementation decreased not only the production of inflammatory cytokines but also that of oxidative stress markers, as we previously reported (19,29).”
From Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress (2007) · cites this paper as [29]
In the citing paper
“Zinc deficiency affects T helper subset 1 cell function adversely in humans (36–38, 43).”
From Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease (2013) · cites this paper as [43]
In the citing paper
“The intracellular zinc concentration, such as the lymphocyte zinc concentration, is a better indicator of zinc status as we previously reported (4,6).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Wyllie, A. H. (1980) · Nature · doi:10.1038/284555a0 · Cited by 4,495
Modern Nutrition in Health and Disease.
(1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-108-3-508_7 · Cited by 3,381
The biochemical basis of zinc physiology
Vallée, B. L., & Falchuk, K. H. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.1.79 · Cited by 3,005
Cousins, R. J. (1985) · Physiological Reviews · doi:10.1152/physrev.1985.65.2.238 · Cited by 1,331
Apoptosis And Programmed Cell Death In Immunity
Cohen, J., Duke, R. C., Fadok, V. A., & Sellins, K. S. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.001411 · Cited by 1,112
Romagnani, S. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80019-9 · Cited by 1,072
ZINC PROTEINS: Enzymes, Storage Proteins, Transcription Factors, and Replication Proteins
Coleman, J. E. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.004341 · Cited by 980
Fosmire, G. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/51.2.225 · Cited by 907
The physiological role of zinc as an antioxidant
Bray, T. Μ., & Bettger, W. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90076-u · Cited by 896
Palmiter, R. D., & Findley, S. D. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07042.x · Cited by 758
Research works printed but not linked: 16
- Zalewski, 1996, Zinc and immunity: implications for growth, survival and function of lymphoid cells, J Nutr Immunol, 4, 39
- Pekarek, 1977, Humoral and cellular immune response in zinc-deficient rats, Nutr Rep Int, 16, 267
- Shankar, 1995, Zinc-deficiency exacerbates experimental malaria infection in mice, FASEB J, 9, A4269
- Shankar, 1997, Zinc supplementation can reduce malaria-related morbidity in preschool children, Am J Trop Med Hyg, 57, A434
- Fraker, 1981, Immune repair capacity of zinc deficient young adult and neonatal mice, Fed Proc, 40, 918
- Arif, 1987, Effect of zinc diet on Xanthine oxidase activity of liver of mice infected with Plasmodium berghei, Indian J Malariol, 24, 59
- Tapazoglou, 1985, Decreased natural killer cell activity in zinc deficient subjects with sickle cell disease, J Lab Clin Med, 105, 19
- Cunningham-Rundles, 1979, Increased T-lymphocyte function and thymopoietin following zinc repletion in man, Fed Proc, 38, 1222
- Kaplan, 1988, Impaired interleukin 2 production in the elderly: association with mild zinc deficiency, J Trace Elem Exp Med, 1, 3
- Brummerstedt, 1971, The effect of zinc on calves with hereditary thymic hypoplasia (lethal trait A 46), Acta Pathol Microbiol Scand, 79, 686
- Haas, 1976, The effect of zinc deficiency on the immune response of A/J mice, Fed Proc, 35, 659
- Wirth, 1989, Zinc requirements for macrophage function: effect of zinc deficiency on uptake and killing of a protozoan parasite, Immunology, 68, 114
- Prasad, 1997, Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer in non-cancer subjects, Proc Assoc Am Physicians, 109, 68
- Blazsek, 1984, Zinc and immunity, Biomed Pharmacother, 38, 187
- Good, 1982, Effect of undernutrition on host cell and organ function, Cancer Res, 42, 737
- Chvapil, 1972, Pathophysiology of zinc. In: International review of neurobiology, 105
Cited by
Sorted by citations
Maternal and child undernutrition: global and regional exposures and health consequences
Black, R. E., Allen, L. H., Bhutta, Z. A., Caulfield, L. E., de Onis, M., Ezzati, M., Mathers, C., & Rivera, J. (2008) · The Lancet · doi:10.1016/s0140-6736(07)61690-0 · Cited by 6,443
Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease
Prasad, A. S. (2013) · Advances in Nutrition · doi:10.3945/an.112.003210 · Cited by 919
Self-citationGuarino, A., Ashkenazi, S., Gendrel, D., Lo Vecchio, A., Shamir, R., & Szajewska, H. (2014) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000000375 · Cited by 935
Zinc and its role in immunity and inflammation
Bonaventura, P., Benedetti, G., Albarède, F., & Miossec, P. (2015) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.11.008 · Cited by 798
Bhutta, Z. A., Black, R. E., Brown, K. H., Gardner, J. M., Gore, S., Hidayat, A., Khatun, F., Martorell, R., Ninh, N. X., Penny, M. E., et al. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70086-7 · Cited by 731
Self-citationPrasad, A. S., Beck, F. W., Bao, B., Fitzgerald, J. T., Snell, D. C., Steinberg, J. D., & Cardozo, L. J. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.3.837 · Cited by 516
Self-citationClinical, immunological, anti-inflammatory and antioxidant roles of zinc
Prasad, A. S. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2007.10.013 · Cited by 454
Self-citationImmune-enhancing role of vitamin C and zinc and effect on clinical conditions
Wintergerst, E. S., Maggini, S., & Hornig, D. H. (2006) · Annals of Nutrition and Metabolism · doi:10.1159/000090495 · Cited by 418
Bao, B., Prasad, A. S., Beck, F. W., Fitzgerald, J. T., Snell, D., Bao, G. W., Singh, T., & Cardozo, L. J. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.28836 · Cited by 400
Self-citationYakoob, M. Y., Theodoratou, E., Jabeen, A., Imdad, A., Eisele, T. P., Ferguson, J., Jhass, A., Rudan, I., Campbell, H., Black, R. E., et al. (2011) · BMC Public Health · doi:10.1186/1471-2458-11-s3-s23 · Cited by 312
Calder, P. C. (2013) · Proceedings of The Nutrition Society · doi:10.1017/s0029665113001286 · Cited by 283
Zinc: Dietary intake and impact of supplementation on immune function in elderly
Mocchegiani, E., Romeo, J., Malavolta, M., Costarelli, L., Giacconi, R., Diaz, L.-E., & Marcos, A. (2013) · AGE · doi:10.1007/s11357-011-9377-3 · Cited by 198
Bao, B., Prasad, A. S., Beck, F. W. J., Snell, D., Suneja, A., Sarkar, F. H., Doshi, N., Fitzgerald, J. T., & Swerdlow, P. (2008) · Translational Research · doi:10.1016/j.trsl.2008.06.001 · Cited by 187
Self-citationSerum zinc and pneumonia in nursing home elderly
Meydani, S. N., Barnett, J. B., Dallal, G. E., Fine, B. C., Jacques, P. F., Leka, L. S., & Hamer, D. H. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.1167 · Cited by 155
Bhandari, N., Bahl, R., Taneja, S., Strand, T., Mølbak, K., Ulvik, R. J., Sommerfelt, H., & Bhan, M. K. (2002) · PEDIATRICS · doi:10.1542/peds.109.6.e86 · Cited by 158
Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity
Cassat, J. E., & Skaar, E. P. (2012) · Seminars in Immunopathology · doi:10.1007/s00281-011-0294-4 · Cited by 155
Low zinc status: a new risk factor for pneumonia in the elderly?
Barnett, J. B., Hamer, D. H., & Meydani, S. N. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2009.00253.x · Cited by 149
An Antimicrobial Role for Zinc in Innate Immune Defense Against Group A Streptococcus
Ong, C.-L. Y., Gillen, C. M., Barnett, T. C., Walker, M. J., & McEwan, A. G. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiu053 · Cited by 124
Nazarizadeh, A., & Asri-Rezaie, S. (2016) · AAPS PharmSciTech · doi:10.1208/s12249-015-0405-y · Cited by 135
Bresnahan, K. A., & Tanumihardjo, S. A. (2014) · Advances in Nutrition · doi:10.3945/an.114.006361 · Cited by 132
Serum copper and zinc levels in individuals with autism spectrum disorders
Li, S.-O., Wang, J.-L., Bjørklund, G., Zhao, W.-N., & Yin, C.-H. (2014) · NeuroReport · doi:10.1097/wnr.0000000000000251 · Cited by 121
Savino, W., & Dardenne, M. (2010) · Proceedings of The Nutrition Society · doi:10.1017/s0029665110002545 · Cited by 109
Bhatnagar, S., Wadhwa, N., Aneja, S., Lodha, R., Kabra, S. K., Natchu, U. C. M., Sommerfelt, H., Dutta, A. K., Chandra, J., Rath, B., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60477-2 · Cited by 90
Metallothionein: a Potential Link in the Regulation of Zinc in Nutritional Immunity
Rahman, M. T., & Karim, M. M. (2018) · Biological Trace Element Research · doi:10.1007/s12011-017-1061-8 · Cited by 77
Zinc and Diabetes: A Connection between Micronutrient and Metabolism
Ahmad, R., Shaju, R., Atfi, A., & Razzaque, M. S. (2024) · Cells · doi:10.3390/cells13161359 · Cited by 77
Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months
Lassi, Z. S., Haider, B. A., & Bhutta, Z. A. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005978.pub2 · Cited by 71
Effect of transfusional iron overload on immune response.
Cunningham‐Rundles, S., Giardina, P. J., Grady, R. W., Califano, C., McKenzie, P., & De Sousa, M. (2000) · The Journal of Infectious Diseases · doi:10.1086/315919 · Cited by 71
Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis
Kim, J., Yoo, S., Jeong, M., Ko, J., & Ro, Y. (2014) · Acta Dermato Venereologica · doi:10.2340/00015555-1772 · Cited by 71
Prasad, A. S., Bao, B., Beck, F. W. J., & Sarkar, F. H. (2002) · Journal of Laboratory and Clinical Medicine · doi:10.1067/mlc.2002.127908 · Cited by 65
Self-citationNew Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A Streptococcal Infection
Ong, C.-L. Y., Berking, O., Walker, M. J., & McEwan, A. G. (2018) · Infection and Immunity · doi:10.1128/iai.00048-18 · Cited by 54
Strand, T. A., Hollingshead, S. K., Julshamn, K., Briles, D. E., Blomberg, B., & Sommerfelt, H. (2003) · Infection and Immunity · doi:10.1128/iai.71.4.2009-2013.2003 · Cited by 44
Darling, A. M., Mugusi, F. M., Etheredge, A. J., Gunaratna, N. S., Abioye, A. I., Aboud, S., Duggan, C., Mongi, R., Spiegelman, D., Roberts, D., et al. (2017) · The American Society of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.16-0599 · Cited by 33
Xue, Y., Osborn, J., Panchal, A., & Mellies, J. L. (2015) · Applied and Environmental Microbiology · doi:10.1128/aem.00507-15 · Cited by 18
Metadata
- Authors
- Shankar, A. H., & Prasad, A. S.
- Affiliations
- Johns Hopkins University (US)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 68
- Issue
- 2
- Pages
- 447S-463S
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W1943607432
- Cited by
- 1,606
- References
- 250
- Citations by year
- 2026: 33 · 2025: 53 · 2024: 46 · 2023: 52 · 2022: 70 · 2021: 90 · 2020: 98 · 2019: 65 · 2018: 52 · 2017: 77 · 2016: 84 · 2015: 61 · 2014: 91 · 2013: 70 · 2012: 68
- FWCI
- 8.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University (HRN-A-00-97-00015-00)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- zinc, zinc deficiency, immune function, infection susceptibility, non-specific immunity, natural killer cells, neutrophils, T cell activation, Th1 cytokines, B cells, antibody production, IgG, macrophages, phagocytosis, apoptosis, antioxidant function, zinc supplementation
- MeSH terms
- Animals, Glucocorticoids, Humans, Immunity, Infections, Thymic Factor, Circulating, Zinc, Cytokines, Apoptosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
