Published in PLOS One on 2026-05-18, this study is presented as an attributed evidence briefing. The excerpts below are the original researchers’ words, reproduced under their Creative Commons Attribution licence. Health Signal has selected the abstract and, where needed, opening background paragraphs; the complete methods, results, limitations and references remain in the linked paper.
Original authors: David Chisompola, Emmanuel Luwaya, Martin Chakulya, Joseph M Chalwe, Joreen P Povia, Annet Kirabo, Sepiso K Masenga
Source: PLOS One • DOI 10.1371/journal.pone.0341044
Read the complete primary study ↗ · Creative Commons Attribution licence
From the researchers
Abstract
Interleukin-17A (IL-17A) is a key Th17 cytokine involved in mucosal defense and chronic inflammation and serves as an important biomarker and therapeutic target in autoimmune, cardiovascular, and infectious diseases. Emerging evidence indicates that immune regulation may differ by sex, which may influence disease susceptibility, biomarker interpretation, and treatment response. However, few studies have examined sex-specific determinants of IL-17A. This study aimed to identify the sociodemographic, clinical, and inflammatory correlates of circulating IL-17A, with a specific focus on elucidating sex-specific determinants.
We conducted a cross-sectional study in a cohort of adults attending routine clinic from Livingstone University Teaching Hospital in Zambia. Plasma levels of IL-17A and a panel of inflammatory cytokines were measured. Sociodemographic, metabolic and clinical data, including HIV status and ART regimen, were collected. Sex-stratified multiple linear regression models were used to identify independent correlates of IL-17A levels with statistical significance p < 0.05.
A total of 225 participants were recruited, comprising 71 males and 154 females, with median ages 50 (41, 59) vs. 48 (40, 58) years, respectively. Distinct sex-specific factors associated with IL-17A were identified. In males, IL-17A levels were significantly associated with a recognized inflammatory cytokine network, including positive correlations with IL-6 (Beta: 43.96, 95% CI: 30.58–57.34, p < 0.001) and IL-1β (Beta: 0.02, 95% CI: 0.02–0.03, p < 0.001), and a negative association with IFN-γ (Beta: −1.21, 95% CI: −1.65 – −0.77, p < 0.001). However, living with HIV was not a predictor of IL-17A (Beta: −1248.07, 95% CI: −2752.35–256.21, p = 0.101). Among females, none of the cytokines or HIV status predicted IL-17A; instead, plasma potassium (Beta: 9.81, 95% CI: 5.31–14.30, p < 0.001) was the only significant determinant of IL-17A.
The determinants of IL-17A are fundamentally different between males and females. These findings underscore the importance of considering biological sex as a key variable in immunology research. They suggest that IL-17A may require sex-specific interpretation as a biomarker of inflammation, particularly in HIV-associated and cardiometabolic conditions, and highlight the potential for sex-tailored therapeutic strategies targeting IL-17A-related pathways. Further studies are needed to validate these findings and explore their mechanistic and clinical implications.
Introduction
Interleukin-17A (IL-17A) is a key cytokine orchestrating host defense, inflammation, and autoimmune pathology, primarily produced by T-helper 17 (Th17) cells [1]. Its production is classically regulated by a network of inflammatory cytokines, including IL-6 and IL-1β, which promote Th17 differentiation, and IFN-γ, which can antagonize this pathway [2,3]. While IL-17A is a well-established mediator in chronic inflammatory and autoimmune conditions, its regulation in the context of hypertension, human immunodeficiency virus (HIV) infection and the potential influence of biological sex remains incompletely understood.
Reading this evidence
Use the full paper to check the study design, participant selection, comparator and outcome definitions before drawing a practical conclusion. An association does not by itself show cause and effect. A reported performance measure needs its denominator and uncertainty. A finding from a particular facility, sample or time period should retain that scope when it is discussed elsewhere.
This briefing makes the source accessible within the wider hospital systems desk. It does not assess an individual patient or certify a product. When considering relevance to another health system, examine the original authors’ account of context and limitations, then seek local implementation evidence. The related reporting below provides other studies to read alongside this one; it is a topic connection, rather than a claim that their results are directly comparable.
© 2026 David Chisompola, Emmanuel Luwaya, Martin Chakulya, Joseph M Chalwe, Joreen P Povia, Annet Kirabo, Sepiso K Masenga. Excerpts reproduced under CC BY. Selection, formatting and contextual notes by Health Signal. The researchers are the authors of the source study, not members of Health Signal’s staff.
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