Introduction: The dysregulated immune response in
sepsis is highly variable, ranging from hyperinflammation to immunoparalysis.
Obesity is associated with the release of inflammatory mediators from adipose tissue, known as
adipocytokines, causing a chronic inflammatory state. Perhaps counterintuitively,
obesity is also associated with lower mortality in
sepsis patients. We investigated the association between
obesity, circulating
adipocytokine concentrations, immune dysregulation, and outcome in
sepsis patients. Methods In this secondary analysis of a prospective study, plasma concentrations of the
adipocytokines leptin,
adiponectin, and
resistin were assessed in 167 patients at diagnosis of
sepsis due to
pneumonia,
bacteremia, or acute
cholangitis.
Adipocytokines were compared between patients with normal
weight (body mass index [BMI], 18.5-24.9 kg/m 2 ; n = 67),
overweight (BMI, 25.0-29.9 kg/m 2 ; n = 56), and
obesity (BMI ≥30 kg/m 2 ; n = 42), as well as between immunological endotypes: hyperinflammation (n = 40), immunoparalysis (n = 62), and unclassified (n = 55). Results: Higher circulating concentrations of
leptin were observed in patients with
obesity compared with patients with normal weight ( P = 0.008) and
overweight ( P = 0.02), whereas
adiponectin and
resistin plasma concentrations were not different ( P = 0.08 and P = 0.85, respectively).
Resistin concentrations were associated with immunological endotypes, with the highest levels found in hyperinflammatory patients ( P < 0.001). Furthermore,
resistin concentrations were predictive for 28-day mortality (adjusted odds ratio, 1.03 per 10 ng/mL; P = 0.04). These associations were not found for
leptin and
adiponectin. Conclusion:
Obesity and BMI-related
adipocytokines are not related to the development of a hyperactive or suppressed immune response as defined by
ferritin and mHLA-DR expression in
sepsis patients. Although
resistin is related to the immune response and an increased risk of adverse clinical outcomes, these associations are similar in patients with normal weight,
overweight, and
obesity. This implies that the relationship between
resistin and clinical outcome is likely driven by the inflammatory response and not by
obesity itself. Taken together, although there exists a strong association between
inflammation and
sepsis mortality, our results do not point toward a role for
obesity and BMI-related
adipocytokines in immune dysregulation in
sepsis patients.