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Cytokine Levels in Patients with and without Fungal Infections
Amani Politano, Laura Rosenberger, Matthew McLeod, Tjasa Hranjec, Lesle Dossett, Addison May, and Robert Sawyer. University of Virginia
Background: Interventions targeting specific immune responses to infections have yet to be successful, likely due to heterogeneity of sites, patient factors, and pathogens. Previous studies have suggested that Candida infections are associated with increased IL-1, -6, and -8 expression, and that elevated IL-4 and -10 expression contributes to mortality. Hypothesis: We hypothesize that ICU -acquired Candida infections are associated with specific elevations in cytokines, including IL-1, -8, -10, and TNFα, when compared to bacterial infections. Methods: ICU-acquired infections were identified in trauma/surgical patients. Serum samples collected within 48 h of diagnosis were analyzed for IL-1, -2, -4, -6, -8, -10, -12, IFN?, GM-CSF, and TNFα by ELISA. Demographics, outcomes, and cytokine levels were compared using independent samples t-test, χ2, and Mann-Whitney U tests. Results: 933 infections were identified, including 138 with Candida or yeast isolated. Demographics and outcomes are shown. Patients with fungal infections had elevated IL-8 and GM-CSF (52.5 [15.5, 99.7] vs. 32.0 [11.6, 71.5], p=0.011; 2.7 [2.7, 6.8] vs. 3.4 [2.7, 9.0], p=0.009). Positive fungal cultures were significantly more common in patients with abdominal, urine, skin structure, or catheter-associated infections, and significantly less common in lung infections (p<0.007 for all). Mortality did not differ by presence of fungi. However, patients with fungal infections who died had significantly elevated IL-1, -8, and -10 expression (p<0.03 for all). Patients without fungi who died had elevated IL-4, -6, -8, -10, and TNFα (p<0.02 for all). Conclusions: Cytokine expression varies according to specific bacterial pathogens in animal models. Our data show that IL-8 and GM-CSF expression differs between infected patients with and without fungi. In addition, the cytokine response differs significantly in patients who die, suggesting a dysregulated immune response in these patients. Further studies are required to determine whether these changes are site- or species-specific, and to evaluate potential targeted interventions. 
Mean ± standard error or n (%).
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