Neutrophil Lymphocyte Ratio

The treasure trove of blood chemistry… Neutrophil Lymphocyte Ratio (NLR)

By Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

Blood carries everything from nutrients and oxygen, to clues that help practitioners solve the puzzle of disease and dysfunction. This is where functional blood chemistry analysis can help more fully evaluate a patient’s condition.

Using a readily available CBC with differentiation report, a practitioner can assess the neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammation associated with more severe disease and complications.

In general, a higher NLR correlates with poor prognosis and higher mortality rates, even when white blood cell count is normal.[1] Elevated NLR is associated with an increased probability of bacterial infection and lower probability of viral infection.[3]

Neutrophils and lymphocytes participate in cell-mediated inflammatory responses and an increased NLR is associated with elevated inflammatory markers including tumor necrosis factor alpha, IL-6, IL7, IL-8, IL-12, and IL-17. [4]

Accumulating research suggests an association between an elevated NLR and worse outcomes for several cancers including breast, ovarian, gastroesophageal, pancreas, colon, colorectal, hepatocellular, biliary tract, kidney, and urothelium.[5] [6] [7] An elevated NLR also appears to reflect more aggressive disease associated with advanced tumor stage and metastases and reduced overall survival[8] [9] [10]

Increased ratio of neutrophils to lymphocytes is also observed in congestive heart failure, atherosclerotic changes, cardiovascular disease, diabetes mellitus, hypertension, severe acute pancreatitis, sepsis, and septic shock.[11] [12] [13] [14] [15] [16]

Individuals with bipolar disorder and major depressive disorder were found to have elevated NLR values as well, likely a reflection of the inflammatory nature of these mood disorders.[17] [18]

Although some associations have been observed, further research is recommended to investigate the association between elevated NLR, cognitive decline, and Alzheimer’s disease.[19] [20] [21]

Clinicians should investigate NLR values of greater than 2.2 in order to identify the potential significance of neutrophil lymphocyte ratios in their patients. A detailed account of a patient’s medical history and current symptomatology, along with further blood chemistry analysis, will help bring a patient’s full clinical picture into focus.

References

[1] Lee JS, Kim NY, Na SH, et al. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018 Jun;97(26) [R]

[2] Gürağaç A, Demirer Z. The neutrophil-to-lymphocyte ratio in clinical practice. Can Urol Assoc J. 2016 Mar-Apr;10(3-4) [R]

[3] Naess A, Nilssen SS, Mo R, et al. Role of neutrophil to lymphocyte and monocyte to lymphocyte ratios in the diagnosis of bacterial infection in patients with fever. Infection. 2017 Jun;45(3):299-307. [R]

[4] Venkatraghavan L, Tan TP, Mehta J, et al. Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation – A cross-sectional study in a pre-admission setting. F1000Res. 2015 May 22;4:123 [R]

[5] Faria SS, Fernandes PC Jr, Silva MJ, et al. The neutrophil-to-lymphocyte ratio: a narrative review. Ecancermedicalscience. 2016 Dec 12;10:702. [R]

[6] Gürağaç A, Demirer Z. The neutrophil-to-lymphocyte ratio in clinical practice. Can Urol Assoc J. 2016 Mar-Apr;10(3-4):141. [R]

[7] McNamara MG, Templeton AJ, Maganti M, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014 Jun;50(9):1581-9. [R]

[8] Guthrie GJ, Charles KA, Roxburgh CS, et al The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients 0with cancer. Crit Rev Oncol Hematol. 2013 Oct;88(1):218-30. [R]

[9] Sahin AG, Aydin C, Unver M, et al. Predictive Value of Preoperative Neutrophil Lymphocyte Ratio in Determining the Stage of Gastric Tumor. Med Sci Monit. 2017 Apr 24;23:1973-1979. [R]

[10] Bowen RC, Little NAB, Harmer Jr, et al. Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis. Oncotarget. 2017 May 9;8(19):32171-32189 [R]

[11] Imtiaz F, Shafique K, Mirza SS, et al. Neutrophil lymphocyte  ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012 Jan 26;5(1):2 [R]

[12] Wang Y, Fuentes HE, Attar BM, et al. Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis. Pancreatology. 2017 Nov -Dec;17(6):893-897. [R]

[13] Venkatraghavan L, Tan TP, Mehta J, et al. Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation – A cross-sectional study in a pre-admission setting. F1000Res. 2015 May 22;4:123. [R]

[14] 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 Aug;19(8):780-785. [R]

[15] Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. Expert Rev Cardiovasc Ther. 2016;14(5):573-7. [R]

[16] Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 2001;102(1):5-14. English, Slovak. [R]

[17] Mazza MG, Lucchi S, Tringali AGM, et al. Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):229-236. [R]

[18] Giynas Ayhan, M., Cicek, I. E., Inanli, I., Caliskan, A. M., Kirci Ercan, S., & Eren, I. (2017). Neutrophil/lymphocyte and platelet/lymphocyte ratios in all mood states of bipolar disorder. Psychiatry and Clinical Psychopharmacology, 27(3), 284-288. [R]

[19] Kuyumcu ME, Yesil Y, Oztürk ZA, et al. The evaluation of neutrophil-lymphocyte ratio in Alzheimer's disease. Dement Geriatr Cogn Disord. 2012;34(2):69-74. [R]

[20] Rembach A, Watt AD, Wilson WJ, et al; AIBL Research Group. An increased neutrophil-lymphocyte ratio in Alzheimer's disease is a function of age and is weakly correlated with neocortical amyloid accumulation. J Neuroimmunol. 2014 Aug 15;273(1-2):65-71. [R]

[21] Halazun HJ, Mergeche JL, Mallon KA, et al. Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients. J Vasc Surg. 2014 Mar;59(3):768-73. [R]

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