Sex and race differences in urinary Tumor Necrosis Factor-α (TNF-α) levels: Secondary analysis of the DASH-sodium trial

• Published in: Journal of human hypertension Vol. 37; no. 8; pp. 701 - 708
• Main Authors: Drugge, Elizabeth D., Farhan, Khalid, Zhao, Hong, Abramov, Rozalia, Graham, Lesley A., Stambler, Nancy, Hao, Shoujin, Ferreri, Nicholas R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2023; Nature Publishing Group
• Subjects: 631/443/592/75/243/785; 631/80; 82/51; Animal models; Blood pressure; Diet; Dietary intake; Epidemiology; Females; Health Administration; Homeostasis; Hypertension; Males; Medicine; Medicine & Public Health; Public Health; Racial differences; Sodium; Sodium chloride; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1476-5527; 0950-9240; 1476-5527
• DOI: 10.1038/s41371-022-00748-z

Previous work in mouse models shows that urinary TNF-α levels become elevated when dietary salt (NaCl) intake increases. To examine if this relationship exists in humans, we conducted a secondary analysis of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine levels of urinary TNF-α in 367 subjects categorized by race, sex, and blood pressure. The DASH-Sodium trial is a multicenter feeding trial in which subjects were randomly assigned to either the DASH or control diet, and high, medium, and low sodium in random order. Multivariable linear regression was used to model baseline TNF-α and a mixed model was used to model TNF-α as a function of dietary intervention. At baseline, with all subjects on a “typical American diet”, urinary TNF-α levels were lowest in Black, p  = 0.002 and male subjects, p  < 0.001. After randomization to either the DASH or control diet, with increasing levels of sodium, urinary TNF-α levels increased only in subjects on the control diet, p  < 0.05. As in the baseline analysis, TNF-α levels were highest in White females, then White males, Black females and lowest in Black males. The results indicate that urinary TNF-α levels in DASH-Sodium subjects are regulated by NaCl intake, modulated by the DASH diet, and influenced by both race and sex. The inherent differences between subgroups support studies in mice showing that increases in renal TNF-α minimize the extent salt-dependent activation of NKCC2. Baseline conditions- Blacks/Males ingesting a “Typical American Diet” exhibited lower urinary tumor necrosis factor-α (TNF-α) levels than Whites/Females, likely contributing to higher Na + - K + -2Cl - cotransporter type 2 (NKCC2) activity as previously suggested for Black vs White individuals. Higher urinary TNF-α in Females may be required to suppress inherently higher NKCC2 activity to maintain homeostasis. After randomization- Urinary TNF-α increased only for those on the high sodium & control diet, an effect which appeared to be attenuated for those on the Dietary Approaches to Stop Hypertension (DASH) diet.