Vitamin D, thyroid hormones and muscle mass influence natural killer (NK) innate immunity in healthy nonagenarians and centenarians

Abstract

Increasing evidence has demonstrated that the immune system closely interacts with other physiological systems, whose communications are mediated by circulating cytokines and hormones. The aim of our study was to test whether the number and cytolytic activity of NK cells in a group of relatively healthy Italian nonagenarians and centenarians were affected by the modifications of endocrine, metabolic and functional parameters that occur during ageing. Because of the extreme age of the study population, a cross-sectional analysis was performed. This study revealed that the group of oldest subjects with the highest number of NK cells and the best preserved cytolytic function also presented a preserved metabolism of thyroid hormones and vitamin D and integrity of muscle mass. In fact, the NK cell number and/or cytolytic activity of healthy subjects > 90 years old was positively associated with serum levels of vitamin D, while T3, FT4, i-PTH hormones and lean body mass were associated only with NK cell number. In conclusion, our results stress the paramount importance of nutritional evaluation in the clinical assessment of elderly people.

Fig 1

Functional activity of NK cells and phenotypical distribution of CD16 and CD56 lymphocytes in the peripheral blood of elderly subjects. (a) Results are expressed as mean percentages of ⁵¹Cr release ± s.e.m. of women (•) and men (○). (b) Results are expressed as mean percentages of positive CD16 (▪) and CD56 (▴) lymphocytes ± s.e.m. (boxes), range values are represented by whiskers.

Fig 2

Multiple scatterplot between T and NK lymphocytes and between NK lymphocytes and cytolytic activity. (a) A direct correlation was found between CD16 and CD56 cell numbers (• and continuous line) (Pearson's coefficient r = 0.64, P < 0.001), while an inverse correlation was noted between CD16 and CD3 cell numbers (○ and dashed line) (Pearson's coefficient r = −0.28, P < 0.05). (b) CD16 cell numbers were also related to cytolytic activity (Pearson's coefficient r = 0.29, P < 0.05), following a quadratic curve (R² = 0.85, s.e.m. = 18.9, P < 0.01). E/T100 corresponds to the percentage of ⁵¹Cr release obtained from 100:1 effector:target cell ratio.

Fig 3

Multiple scatterplot between NK lymphocytes and thyroid hormones. CD16 cell numbers were directly correlated with T₃ (Pearson's coefficient r = 0.28, P < 0.05) (• and continuous line) and FT₄ (Pearson's coefficient r = 0.34, P < 0.01) (○ and dashed line).

Fig 4

Multiple scatterplot between NK lymphocytes and DHT. C D 16 cell numbers were directly correlated with dihydrotestosterone (DHT) (Pearson's coefficient r = 0.86, P < 0.001) (• and continuous line).

Fig 5

Multiple scatterplot among NK lymphocytes, vitamin D and intact parathyroid hormone (i-PTH). (a) A direct correlation was found between CD16 cell numbers and vitamin D (Pearson's coefficient r = 0.40, P < 0.01), following a quadratic curve (R² = 0.86, s.e.m. = 7.3, P < 0.01), while an inverse correlation (b) was noted between CD16 cell numbers and i-PTH (Pearson's coefficient r = –0.33, P < 0.05). (c) Vitamin D was also related to cytolytic activity (Pearson's coefficient r = 0.33, P < 0.05), following a logarithmic curve (R² = 0.83, s.e.m. = 20.3, P < 0.001). E/T100 corresponds to the percentage of ⁵¹Cr release obtained from 100:1 effector:target cell ratio.

Fig 6

Multiple scatterplot among anthropometric parameters, NK lymphocytes, vitamin D and age. (a) A conserved muscular mass (AMA) was positively correlated with increasing CD16 cell numbers (Pearson's coefficient r = 0.35, P < 0.01) (• and continuous line) but negatively with age (Pearson's coefficient r = –0.30, P < 0.05) (○ and dashed line). (b) AFA (• and continuous line) and TST (○ and dashed line) fat reserves were directly linked to vitamin D (Pearson's coefficient r = 0.47, P < 0.01 for both).