Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study

Raffaello Pellegrino; Roberto Paganelli; Angelo Di Iorio; Stefania Bandinelli; Antimo Moretti; Giovanni Iolascon; Eleonora Sparvieri; Domiziano Tarantino; Luigi Ferrucci

doi:10.1186/s12979-023-00370-8

Temporal trends, sex differences, and age-related disease influence in Neutrophil, Lymphocyte count and Neutrophil to Lymphocyte-ratio: results from InCHIANTI follow-up study

Immun Ageing. 2023 Sep 4;20(1):46. doi: 10.1186/s12979-023-00370-8.

Authors

Affiliations

¹ Department of Scientific Research, Off-Campus Semmelweis University, Campus Ludes, 6912, Lugano-Pazzallo, Switzerland.
² Saint Camillus International University of Health and Medical Sciences, Rome, Italy.
³ Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Viale Abruzzo 322, 66100, Chieti-Pescara, Italy. angelo.diiorio@unich.it.
⁴ Geriatric Unit, Azienda Toscana Centro, Florence, Italy.
⁵ Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
⁶ Department of Internal Medicine, ASL Teramo, Teramo, Italy.
⁷ Department of Public Health, University of Naples Federico II, 80131, Naples, Italy.
⁸ Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 21224, Baltimore, MD, USA.

^# Contributed equally.

Abstract

Background: Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years' follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population.

Methods: The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session.

Results: The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants.

Conclusion: NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.

Keywords: Aging; Gender-dimorphism; Longitudinal study; Lymphocytes; Neutrophils; Neutrophils-to-Lymphocytes-ratio; Observational study; Temporal-trends.

Abstract

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