Resistin induces insulin resistance in mice. In humans, recent data suggest that resistin functions as a proinflammatory cytokine. Here, we studied resistin up to 2 wks after admission in patients with septic shock and/or severe sepsis.
Two prospective studies of patients with sepsis and in vitro studies of resistin interaction with monocytes.
Intensive care unit at Karolinska University Hospital and Center for Infectious Medicine, Karolinska Institute, Huddinge, Sweden.
Twenty-nine patients with severe sepsis and 66 with septic shock.
Ninety-five patients were studied, 25 of whom died within 28 days. Resistin and cytokine levels and routine biochemistry were measured at three to six defined time points during the first 2 wks after admission and were correlated to other cytokines, glucose levels, body mass index, Acute Physiology and Chronic Health Evaluation II, and Sepsis-related Organ Failure Assessment scores.
Serum resistin was significantly elevated compared with healthy controls (p < .000001) and correlated with severity of disease as measured by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, with an increasingly strong degree of correlation over time. Median levels were four- to eight-fold higher than controls and remained high up to 2 wks after admission to the intensive care unit. Levels correlated with interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α, creatinine, D-dimer, and lactate, but not with p-glucose or body mass index. In vitro, resistin was released from monocytes after stimulation with either lipopolysaccharide or high mobility group box 1 protein. Recombinant resistin itself up-regulated intercellular adhesion molecule-1 on monocytes.
This is the first study assessing systemic levels of resistin in patients with septic shock/severe sepsis. We show that resistin is a marker of severity of disease and possibly a mediator of the prolonged inflammatory state seen in infected critically ill patients. Further exploration of resistin as a therapeutic target and marker of disease is merited.
From the Department of Medicine, Division of Infectious Diseases, Center for Infectious Medicine (JSC, GM, JA, ANT, CJT), and the Department of Anesthesiology (LT), Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden; Department of Medicine, Karolinska Institutet at Södersjukhuset, Stockholm, Sweden (TN); and the Department of Biostatistics, School of Public Health, University of California, Los Angeles, CA (ML).
Supported, in part, by grants from ALF project funding, the Swedish Research Council, the Magnus Bergvalls Foundation, the Swedish Foundation for Strategic Research, the Swedish Society for Medicine, and the Karolinska University Hospital Huddinge Research Foundation.
The authors have not disclosed any commercial or other associations that might pose a conflict of interest.
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