Intersection of Aging and Particulate Matter 2.5 Exposure in Real World: Effects on Inflammation and Endocrine Axis Activities in Rats

Abstract

Exposure to particulate matter 2.5 (PM2.5) is detrimental to multiple organ systems. Given the factor that aging also alters the cellularity and response of immune system and dysfunction of hypothalamic-pituitary-adrenal, -gonad and -thyroid axes, it is imperative to investigate whether chronic exposure to PM2.5 interacts with aging in these aspects. In this study, two-months-old Sprague-Dawley rats were exposed to real world PM2.5 for 16 months. PM2.5 exposure diminished the relative numbers of CD4⁺ T cells and CD8⁺ T cells and increased the relative number of B cells in the peripheral blood of male rats. Conversely, only reduced relative number of CD4⁺ T cells was seen in the blood of female rats. These shifts resulted in elevated levels of proinflammatory factors interleukin-6 and tumor necrosis factor-α in the circulatory systems of both sex, with females also evidencing a rise in interleukin-1β levels. Moreover, heightened interleukin-6 was solely discernible in the hippocampus of female subjects, while increased tumor necrosis factor-α concentrations were widespread in female brain regions but confined to the male hypothalamus. Notable hormonal decreases were observed following PM2.5 exposure in both sex. These comprised declines in biomolecules such as corticotrophin-releasing hormone and cortisol, generated by the hypothalamic-pituitary-adrenal axis, and thyroid-releasing hormone and triiodothyronine, produced by the hypothalamic-pituitary-thyroid axis. Hormonal elements such as gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone, derived from the hypothalamic-pituitary-gonad axis, were also diminished. Exclusive to male rats was a reduction in adrenocorticotropic hormone levels, whereas a fall in thyroid-stimulating hormone was unique to female rats. Decreases in sex-specific hormones, including testosterone, estradiol, and progesterone, were also noted. These findings significantly enrich our comprehension of the potential long-term health repercussions associated with PM2.5 interaction particularly among the aging populace.

Figure 1

Ambient air PM2.5 levels and rat body weight during the 16-month exposure. Monthly mean PM2.5 concentrations during the 16-month exposure period (a). PM2.5 concentrations were measured using an individual particle monitor. Rat body weights were recorded every four months during the 16-month exposure period, beginning at two months of age. Red dotted line presents the average PM2.5 concentration during the exposure period, while green dotted line presents the annual average PM2.5 National Ambient Air Quality Standard in China. (b) Body weights in male and female rats exposed to unfiltered (PM2.5) and filtered air (FA). ^∗∗∗P < 0.001 as compared to male rats exposed to PM2.5. ^#P < 0.05 as compared to female rats exposed to PM2.5 significant, n = 6–9 rats in each group.

Figure 2

Impact of 16-month PM2.5 exposure on peripheral blood lymphocytes. Flow cytometry analysis revealed significant reductions in the proportions of CD4⁺ T cells (CD3⁺CD4⁺) and CD8⁺ T cells (CD3⁺CD8⁺) and increases in the percentage of B cells (CD45RA⁺CD3⁻) in male rats. Conversely, female rats only showed a reduction in the percentage of CD4⁺ T cells. n = 4 rats in each group, ^∗P < 0.05 and ^∗∗∗P < 0.001 for male rats, and ^##P < 0.01 for female rats compared to filtered air (FA) exposure. PM2.5: particulate matter 2.5. (a) Analysis of the proportion of CD4⁺ T cells in the blood. (b) Analysis of the proportion of CD8⁺ T cells in the blood. (c) Analysis of the proportion of B cells in the blood.

Figure 3

Effect of 16-month PM2.5 exposure on serum inflammatory cytokine levels. Male and female rats exposed to PM2.5 exhibited significant elevations in the levels of IL-6, IL-1β, and TNF-α as compared to filtered air (FA) exposure. n = 4 rats in each group, ^∗∗∗P < 0.001 for male rats, and ^###P < 0.001 for female rats as compared to filtered air (FA). PM2.5: particulate matter 2.5. (a) IL-6 level in the blood. (b) IL-1β level in the blood. (c) TNF-α level in the blood.

Figure 4

Impact of 16-month PM2.5 exposure on the mRNA expression levels of inflammatory cytokines in the cortex, hippocampus, and hypothalamus from male and female rats. The exposure to PM2.5 significantly upregulated the mRNA expression levels of these cytokines in the cortex, hippocampus, and hypothalamus of male and female rats. n = 4 rats in each group, ^∗∗∗P < 0.001 for male rats, and ^#P < 0.05 and ^##P < 0.01 for female rats as compared to filtered air (FA) exposure. PM2.5: particulate matter 2.5.

Figure 5

Effect of 16-month PM2.5 exposure on serum hormones levels of hypothalamic-pituitary-adrenal axis in male and female rats. PM2.5 exposure significantly reduced the levels of these hormones in male and female rats. n = 6–8 rats in each group, ^∗∗P < 0.01, ^∗∗∗P < 0.001 for male rats, and ^###P < 0.001 for female rats as compared to filtered air (FA) exposure. CRH: corticotrophin-releasing hormone; ACTH: adrenocorticotropic hormone; and CORT: cortisol. (a) CRH level in the blood. (b) ACTH level in the blood. (c) CORT level in the blood.

Figure 6

Effect of 16-month PM2.5 exposure on the serum hormone levels of hypothalamic-pituitary-thyroid axis in male and female rats. PM2.5 significantly decreased serum levels of TRH and T3 in male and female rats and reduced serum TSH levels in female rats. n = 6–8 rats in each groups, ^∗∗P < 0.01 and ^∗∗∗P < 0.001 for male rats, and ^#P < 0.05 and ^###P < 0.001 for female rats as compared to filtered air (FA) exposure. TRH: thyroid-releasing hormone; TSH: thyroid-stimulating hormone; T3: triiodothyronine (T3); T4: thyroxine (T4); and PM2.5: particulate matter 2.5. (a) TRH level in the blood. (b) TSH level in the blood. (c) T3 level in the blood. (d) T4 level in the blood.

Figure 7

Effect of 16-month PM2.5 exposure on the serum hormone levels of hypothalamic-pituitary-gonad axis in male and female rats. PM2.5 exposure significantly decreased the levels of all hormones, except for T4, in male and female rats. T levels were reduced in male rats, and E2 and PROG levels were reduced in female rats. n = 6–8 rats in each group, ^∗P < 0.05 and ^∗∗P < 0.01, ^∗∗∗P < 0.001 for male rats, and ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 for female rats as compared to filtered air (FA) exposure. GnRH: gonadotropin-releasing hormone, LH: luteinizing hormone; FSH: follicle-stimulating hormone; T: testosterone; E2: estradiol; and PROG: progesterone. (a) GnRH level in the blood. (b) LH level in the blood. (c) FSH level in the blood. (d) T level in the blood. (e) E2 level in the blood. (f) PROG level in the blood.