Resistin levels track sepsis severity and flag higher mortality risk

Sepsis remains one of medicine’s most formidable adversaries, claiming millions of lives worldwide each year despite advances in intensive care. Now, a systematic review and meta-analysis published in BMC Infectious Diseases suggests that a molecule long overshadowed by more famous inflammatory markers may help clinicians identify which sepsis patients are most likely to deteriorate. Resistin, a pro-inflammatory cytokine secreted primarily by monocytes and macrophages, appears to rise in step with sepsis severity, and patients who ultimately die of the condition show markedly higher levels than those who survive.

The research team, led by Youjia Hao and colleagues in the Department of Critical Care Medicine at Beijing Jishuitan Hospital, Capital Medical University, systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to January 2025. They included prospective studies reporting resistin levels in relation to mortality or disease severity in sepsis. After rigorous screening, eighteen studies encompassing 2,197 sepsis patients made it into the final analysis. The review was registered with PROSPERO under CRD42025639277, ensuring methodological transparency from the outset.

Resistin itself has an intriguing biology. Originally named for its proposed role in insulin resistance, the molecule is now recognized as a potent driver of inflammation. Unlike adipose-derived resistin in rodents, human resistin circulates largely from immune cells, and it amplifies the release of tumor necrosis factor and interleukin-6 while promoting endothelial dysfunction. In the context of sepsis, where a dysregulated host response to infection cascades into organ failure, resistin’s rise seems to mirror the intensity of that inflammatory storm.

The meta-analysis quantified this relationship using standardized mean differences, a statistical measure that allows comparison across studies employing different laboratory assays. Resistin levels were significantly higher in non-survivors than in survivors, with a pooled standardized mean difference of 0.83 and a 95 percent confidence interval spanning 0.31 to 1.36. Patients with septic shock, the most severe form of sepsis characterized by profound circulatory collapse, showed even more striking elevations compared to those without shock, with a standardized mean difference of 1.34 and a confidence interval of 0.62 to 2.05. Compared with healthy controls, sepsis patients overall displayed substantially elevated resistin, yielding a standardized mean difference of 1.99 with a confidence interval of 1.63 to 2.35.

When the researchers arranged these findings along the spectrum of disease, a stepwise gradient emerged. Healthy controls occupied the lowest rung, followed by patients with non-shock sepsis, then those with septic shock, and finally non-survivors at the top. This ordered pattern suggests that resistin is not merely a binary flag of infection but a quantitative readout of inflammatory burden, potentially offering clinicians a way to gauge how far along the severity curve a patient sits at the moment of admission.

The team also assessed resistin’s diagnostic accuracy using areas under the receiver operating characteristic curve, a metric that ranges from 0.5, equivalent to random guessing, to 1.0, representing perfect discrimination. The pooled AUC for predicting mortality was 0.68 with a confidence interval of 0.64 to 0.73. In adult patients specifically, the pooled AUC rose to 0.70 with a confidence interval of 0.65 to 0.75. These values indicate moderate discriminatory power, meaning resistin alone cannot reliably sort survivors from non-survivors but may contribute meaningful prognostic information when combined with clinical scoring systems.

However, the analysis was not without caveats. Substantial heterogeneity pervaded the main pooled analyses, reaching an I-squared value of 89 percent, a statistical signal that the included studies varied considerably in their populations, assays, and timing of measurement. The 95 percent prediction intervals for sepsis-related mortality, 28-day mortality, and septic shock all included zero, indicating that the direction of the effect in future studies remains uncertain. Subgroup and meta-regression analyses were conducted to explore potential effect modifiers, but the authors acknowledge that these exploratory tools cannot fully resolve the underlying variability.

The authors conclude that admission resistin levels may be associated with disease severity and adverse outcomes in sepsis, but they are careful to emphasize that clinical utility remains unproven. Their recommendation is unambiguous: large, multicenter prospective studies are needed before resistin can be integrated into routine prognostic assessment. In the interim, the molecule joins a growing list of inflammatory biomarkers, including procalcitonin and interleukin-6, whose prognostic value in sepsis is promising but not yet definitive.

For a condition that kills swiftly and often silently, any tool that sharpens early risk stratification carries enormous clinical weight. Resistin’s stepwise rise across the sepsis spectrum offers a compelling biological narrative, one that aligns with the broader understanding of sepsis as a crescendo of immune dysregulation. Whether this cytokine will earn a place beside lactate and procalcitonin in the emergency department or intensive care unit remains to be seen, but this meta-analysis provides the strongest synthesis to date of its prognostic signal.

The study, published open access under a Creative Commons license, received no specific funding and involved no competing interests. As sepsis continues to challenge clinicians worldwide, biomarkers like resistin represent a frontier where laboratory science meets bedside decision-making, and the coming years of multicenter validation will determine whether this inflammatory messenger becomes a standard component of the sepsis prognostic toolkit.

Subject of Research: The prognostic value of resistin in patients with sepsis: a systematic review and meta-analysis

Article Title: The prognostic value of resistin in patients with sepsis: a systematic review and meta-analysis

Article References: Hao, Y., Bai, Y., Zhang, L., Cui, Z., Liu, C., & Wang, H. (2026). The prognostic value of resistin in patients with sepsis: a systematic review and meta-analysis. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14293-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14293-4

Keywords: resistin, sepsis, biomarker, meta-analysis, septic shock, mortality, inflammation, BMC Infectious Diseases, prognostic, value, patients, systematic