IFN-γ and IL-17A Exhibit Opposing Roles in Age-Related Blood Pressure Dysregulation

Area of Science:

• Immunology and cardiovascular science exploring the interplay between immune system aging, inflammation, and hypertension.
• Investigating age-stratified cytokine profiles and their association with systolic blood pressure (SBP) regulation.
• Examining the influence of HIV status and metabolic factors on immune-driven blood pressure changes.

Background:

• Hypertension involves complex immune pathway interactions, with established roles for IL-6 and TNF-α.
• The specific contributions of T cell cytokines like IFN-γ, IL-17A, and IL-1 to blood pressure regulation in aging populations are less understood.
• Immune senescence, accelerated in people living with HIV (PLWH), may differentially impact age-related blood pressure control.

Purpose of the Study:

• To investigate age-stratified associations between key cytokines (IFN-γ, IL-17A, IL-6, IL-1, TNF-α) and SBP.
• To determine how these cytokine-SBP relationships interact with metabolic factors.
• To compare these associations in people living with HIV (PLWH) and HIV-negative individuals across different age groups.

Main Methods:

• Cross-sectional analysis of 332 adults stratified into two age groups: <45 years and ≥45 years.
• Participants included 241 people living with HIV (PLWH) and 91 HIV-negative individuals.
• Multiple linear regression models assessed SBP associations with plasma cytokine levels, adjusted for demographics, HIV status, LDL cholesterol, and smoking.

Main Results:

• In adults <45 years, SBP was associated with interferon-gamma (IFN-γ) and chronological age.
• In adults ≥45 years, BMI was the dominant SBP predictor, with interleukin-17A (IL-17A) also showing a significant association.
• Cytokine-SBP relationships were consistent across HIV-positive and HIV-negative participants, with IL-6, IL-1, and TNF-α not significantly associated with SBP in either cohort.

Conclusions:

• Blood pressure regulation transitions from immune-driven (IFN-γ in younger adults) to adiposity-driven (BMI and IL-17A in older adults) with advancing age.
• These age-stratified pathophysiological shifts in SBP regulation appear independent of HIV serostatus.
• Findings support the need for age-tailored, mechanism-based approaches to managing blood pressure and related risks.