Differential Systemic MyD88-dependent Versus MyD88- Independent Cytokine Ratio by Etiologic Agent in Adults with Severe Community-Acquired Pneumonia

Purpose: Classifying bacteria early, before cultures results are available, would improve the choice of initial antibiotics in patients with severe pneumonia.TLR2 and TLR4 transduce signal through the MyD88dependent pathway to stimulate IL-8 and TNF-α production.TLR4 can also signal through a MyD88independent pathway to stimulate RANTES and IFN-β production.As gram-negative bacteria primarily activate TLR4, while gram-positive bacteria also activate TLR2, differential cytokine expression would be expected depending on specific bacterial etiologies.Methods: Admission serum samples from 53 patients admitted to the Medical Intensive Care Unit at the University of Maryland Medical Center between January 2006 and September 2013 were assayed for IL-8, RANTES, TNF-α, and IFN-β levels using the University of Maryland cytokine core laboratory and commercial ELISA kits.Cytokine levels and the ratio of MyD88-independent to MyD88-dependent cytokines, ([IFN-α]X[RANTES])/([IL8]X[TNF-α]) were compared to the culture identified organisms.Results: 14 gram-negative and 17 gram-positive pneumonias were identified.None of the individual cytokine demonstrated statistically significant differences between the gram-negative and gram-positive infections.The ratio of MyD88-independent/MyD88-dependent cytokines was 111.1±34.9 in gram-negative infections, 29.9±8.3 in gram-positive infections, with p=0.04.Conclusions: Serum MyD88-independent to MyD88-independentcytokine ratios significantly discriminated gram-negative from gram-positive pneumonia.As technology improves our ability to generate panels of cytokines quickly from clinical specimens, a strategy of pooled cytokine ratios, based on underlying pathophysiology, as was done in our study, could guide clinicians in critical early antibiotic choices.