open access

Vol 77, No 2 (2018)
Review article
Submitted: 2017-06-11
Accepted: 2017-09-11
Published online: 2017-10-23
Get Citation

Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review

P.P. Chmielewski1, B. Strzelec1
·
Pubmed: 29064542
·
Folia Morphol 2018;77(2):171-178.
Affiliations
  1. Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw, Poland

open access

Vol 77, No 2 (2018)
REVIEW ARTICLES
Submitted: 2017-06-11
Accepted: 2017-09-11
Published online: 2017-10-23

Abstract

Total leukocyte count increases significantly in response to infection, trauma, inflammation, and certain diseases. Factors affecting leukocyte count in healthy adults include sex, hormonal milieu, genetic inheritance, stress level, diet, nutrition, and lifestyle (e.g. tobacco-induced inflammatory changes, chronic psychological stress, etc.). To date, numerous studies have reported that high but normal leu­kocyte counts at baseline predict increased cardiovascular and noncardiovascular mortality in older adults. Recent findings suggest that elevated leukocyte count within the normal range, but especially neutrophil and monocyte counts, may be a harbinger of increased systemic inflammation and subclinical disease. Mo­reover, elderly people who tend to have high but normal leukocyte counts are at greater risk of cancer, cardiovascular disease, type 2 diabetes, some other age­-related conditions, and they also have increased all-cause mortality. These results indicate that strong and reliable inflammatory markers, such as leukocyte count, may reflect the rate of ageing and therefore can predict long-term survival in the elderly. Remarkably, leukocyte count correlates positively with genuine markers of systemic inflammation like C-reactive protein and interleukin 6. Interestingly, some authors conclude that leukocyte counts have a stronger prognostic ability with regard to total and cardiovascular mortality than total cholesterol or low­-density lipoproteins. The fact that these inflammatory markers are clinically useful predictors of long-term survival in the elderly is quite remarkable as these blood parameters are included in routine medical check-ups. Therefore, they can be used as simple and reliable morphological indicators of chronic systemic inflammation, disease progression, and poor prognosis, especially among individuals who are likely to develop age-related conditions. Nevertheless, the pathomechanism that links elevated but normal leukocyte counts to increased mortality remains poorly understood. This review summarises the most important findings on the links between leukocyte count, chronic systemic inflammation, and health outcomes in older adults. (Folia Morphol 2018; 77, 2: 171–178)

Abstract

Total leukocyte count increases significantly in response to infection, trauma, inflammation, and certain diseases. Factors affecting leukocyte count in healthy adults include sex, hormonal milieu, genetic inheritance, stress level, diet, nutrition, and lifestyle (e.g. tobacco-induced inflammatory changes, chronic psychological stress, etc.). To date, numerous studies have reported that high but normal leu­kocyte counts at baseline predict increased cardiovascular and noncardiovascular mortality in older adults. Recent findings suggest that elevated leukocyte count within the normal range, but especially neutrophil and monocyte counts, may be a harbinger of increased systemic inflammation and subclinical disease. Mo­reover, elderly people who tend to have high but normal leukocyte counts are at greater risk of cancer, cardiovascular disease, type 2 diabetes, some other age­-related conditions, and they also have increased all-cause mortality. These results indicate that strong and reliable inflammatory markers, such as leukocyte count, may reflect the rate of ageing and therefore can predict long-term survival in the elderly. Remarkably, leukocyte count correlates positively with genuine markers of systemic inflammation like C-reactive protein and interleukin 6. Interestingly, some authors conclude that leukocyte counts have a stronger prognostic ability with regard to total and cardiovascular mortality than total cholesterol or low­-density lipoproteins. The fact that these inflammatory markers are clinically useful predictors of long-term survival in the elderly is quite remarkable as these blood parameters are included in routine medical check-ups. Therefore, they can be used as simple and reliable morphological indicators of chronic systemic inflammation, disease progression, and poor prognosis, especially among individuals who are likely to develop age-related conditions. Nevertheless, the pathomechanism that links elevated but normal leukocyte counts to increased mortality remains poorly understood. This review summarises the most important findings on the links between leukocyte count, chronic systemic inflammation, and health outcomes in older adults. (Folia Morphol 2018; 77, 2: 171–178)

Get Citation

Keywords

ageing, cardiovascular disease, inflammation, leukocyte count, mortality, type 2 diabetes, white blood cells, senescence

About this article
Title

Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review

Journal

Folia Morphologica

Issue

Vol 77, No 2 (2018)

Article type

Review article

Pages

171-178

Published online

2017-10-23

Page views

4034

Article views/downloads

3393

DOI

10.5603/FM.a2017.0101

Pubmed

29064542

Bibliographic record

Folia Morphol 2018;77(2):171-178.

Keywords

ageing
cardiovascular disease
inflammation
leukocyte count
mortality
type 2 diabetes
white blood cells
senescence

Authors

P.P. Chmielewski
B. Strzelec

References (50)
  1. Alexander RW. Inflammation and coronary artery disease. N Engl J Med. 1994; 331(7): 468–469.
  2. Baradaran A, Nasri H, Rafieian-Kopaei M. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J Res Med Sci. 2014; 19(4): 358–367.
  3. Beydoun MA, Beydoun HA, Dore GA, et al. White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults. Transl Psychiatry. 2016; 6(9): e895.
  4. Bonomi M, Patsias A, Posner M, et al. The role of inflammation in head and neck cancer. Adv Exp Med Biol. 2014; 816: 107–127.
  5. Brown DW, Giles WH, Croft JB. White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort. J Clin Epidemiol. 2001; 54(3): 316–322.
  6. Carel RS, Eviatar J. Factors affecting leukocyte count in healthy adults. Prev Med. 1985; 14(5): 607–619.
  7. Chmielewski P. Rethinking modern theories of ageing and their classification: the proximate mechanisms and the ultimate explanations. Anthropol Rev. 2017; 80(3).
  8. Chmielewski P, Borysławski K, Strzelec B. Contemporary views on human aging and longevity. Anthropol Rev. 2016; 79(2).
  9. Chmielewski PP, Borysławski K, Chmielowiec K, et al. The association between total leukocyte count and longevity: Evidence from longitudinal and cross-sectional data. Ann Anat. 2016; 204: 1–10.
  10. Christenson K, Thorén FB, Bylund J. Analyzing cell death events in cultured leukocytes. In: Ashman RB (ed) Leucocytes. Methods and protocols. Humana Press, Springer, New York. 2012: 65–86.
  11. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420(6917): 860–867.
  12. De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009; 15(26): 3003–3026.
  13. Erlinger TP, Muntner P, Helzlsouer KJ. WBC count and the risk of cancer mortality in a national sample of U.S. adults: results from the Second National Health and Nutrition Examination Survey mortality study. Cancer Epidemiol Biomarkers Prev. 2004; 13(6): 1052–1056.
  14. Faria SS, Fernandes PC, Silva MJ, et al. The neutrophil-to-lymphocyte ratio: a narrative review. Ecancermedicalscience. 2016; 10: 702.
  15. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014; 69(Suppl 1): S4–S9.
  16. Franconi F, Rosano G, Basili S, et al. Human cells involved in atherosclerosis have a sex. Int J Cardiol. 2016; 228: 983–1001.
  17. Gkrania-Klotsas E, Ye Z, Cooper AJ, et al. Differential white blood cell count and type 2 diabetes: systematic review and meta-analysis of cross-sectional and prospective studies. PLoS One. 2010; 5(10): e13405.
  18. Grimm RH, Neaton JD, Ludwig W. Prognostic importance of the white blood cell count for coronary, cancer, and all-cause mortality. JAMA. 1985; 254(14): 1932–1937.
  19. Hänsel A, Hong S, Cámara RJA, et al. Inflammation as a psychophysiological biomarker in chronic psychosocial stress. Neurosci Biobehav Rev. 2010; 35(1): 115–121.
  20. Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015; 16(6): 358–372.
  21. Kabat GC, Kim MY, Manson JE, et al. White blood cell count and total and cause-specific mortality in the Women's Health Initiative. Am J Epidemiol. 2017; 186(1): 63–72.
  22. Karabacak M, Turkdogan K, Coskun A, et al. Detection of neutrophil–lymphocyte ratio as a serum marker associated with inflammations by acute carbon monoxide poisoning. J Acute Dis. 2015; 4(4): 305–308.
  23. Leng SX, Xue QL, Huang Yi, et al. Baseline total and specific differential white blood cell counts and 5-year all-cause mortality in community-dwelling older women. Exp Gerontol. 2005; 40(12): 982–987.
  24. Leng S, Xue QL, Huang Yi, et al. Total and differential white blood cell counts and their associations with circulating interleukin-6 levels in community-dwelling older women. J Gerontol A Biol Sci Med Sci. 2005; 60(2): 195–199.
  25. Leng SX, Xue QL, Tian J, et al. Associations of neutrophil and monocyte counts with frailty in community-dwelling disabled older women: results from the Women's Health and Aging Studies I. Exp Gerontol. 2009; 44(8): 511–516.
  26. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006; 83(2): 456S–460S.
  27. Margolis KL, Manson JE, Greenland P, et al. Women's Health Initiative Research Group. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study. Arch Intern Med. 2005; 165(5): 500–508.
  28. Margolis KL, Rodabough RJ, Thomson CA, et al. Women's Health Initiative Research Group. Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women. Arch Intern Med. 2007; 167(17): 1837–1844.
  29. Moradi S, Kerman SR, Rohani F, et al. Association between diabetes complications and leukocyte counts in Iranian patients. J Inflamm Res. 2012; 5: 7–11.
  30. Nam SH, Kang SG, Song SW. The neutrophil-lymphocyte ratio is associated with coronary artery calcification in asymptomatic Korean males: a cross-sectional study. Biomed Res Int. 2017; 2017: 1989417.
  31. Nilsson G, Hedberg P, Ohrvik J. White blood cell count in elderly is clinically useful in predicting long-term survival. J Aging Res. 2014; 2014: 475093.
  32. Pratley RE, Wilson C, Bogardus C. Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender. Obes Res. 1995; 3(6): 563–571.
  33. Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006; 79(3-4): 123–130.
  34. Raman K, Chong M, Akhtar-Danesh GG, et al. Genetic markers of inflammation and their role in cardiovascular disease. Can J Cardiol. 2013; 29(1): 67–74.
  35. Reiss AB, Glass AD. Atherosclerosis: immune and inflammatory aspects. J Investig Med. 2006; 54(3): 123–131.
  36. Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom Med. 2014; 76(3): 181–189.
  37. Ruggiero C, Metter EJ, Cherubini A, et al. White blood cell count and mortality in the Baltimore Longitudinal Study of Aging. J Am Coll Cardiol. 2007; 49(18): 1841–1850.
  38. Sawicki W, Malejczyk J, Wróblewska J. Mechanizmy starzenia: uszkadzanie cząsteczek i zapalenie starcze. Gerentol Pol. 2015; 2: 47–52.
  39. Schaap LA, Pluijm SMF, Deeg DJH, et al. Health ABC Study. Inflammatory markers and loss of muscle mass (sarcopenia) and strength. Am J Med. 2006; 119(6): 526.e9–526.17.
  40. Schaap LA, Pluijm SMF, Deeg DJH, et al. Health ABC Study. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci. 2009; 64(11): 1183–1189.
  41. Shivappa N, Zucchetto A, Montella M, et al. Inflammatory potential of diet and risk of colorectal cancer: a case-control study from Italy. Br J Nutr. 2015; 114(1): 152–158.
  42. Shivappa N, Hébert JR, Rosato V, et al. Inflammatory potential of diet and risk of laryngeal cancer in a case-control study from Italy. Cancer Causes Control. 2016; 27(8): 1027–1034.
  43. Tamakoshi K, Toyoshima H, Yatsuya H, et al. NIPPON DATA90 Research Group. White blood cell count and risk of all-cause and cardiovascular mortality in nationwide sample of Japanese--results from the NIPPON DATA90. Circ J. 2007; 71(4): 479–485.
  44. Tiong AY, Brieger D. Inflammation and coronary artery disease. Am Heart J. 2005; 150(1): 11–18.
  45. Tong PC, Lee KF, So WY, et al. White blood cell count is associated with macro- and microvascular complications in chinese patients with type 2 diabetes. Diabetes Care. 2004; 27(1): 216–222.
  46. Vozarova B, Weyer C, Lindsay RS, et al. High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002; 51(2): 455–461.
  47. Wang H, Hu Y, Geng Y, et al. The relationship between neutrophil to lymphocyte ratio and artery stiffness in subtypes of hypertension. J Clin Hypertens (Greenwich). 2017; 19(8): 780–785.
  48. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005; 115(5): 1111–1119.
  49. Wheeler JG, Mussolino ME, Gillum RF, et al. Associations between differential leucocyte count and incident coronary heart disease: 1764 incident cases from seven prospective studies of 30,374 individuals. Eur Heart J. 2004; 25(15): 1287–1292.
  50. Zvaifler NJ. The immunopathology of joint inflammation in rheumatoid arthritis. Adv Immunol. 1973; 16(0): 265–336.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.: +48 58 320 94 94, faks: +48 58 320 94 60, e-mail: viamedica@viamedica.pl