Research Journal of Infectious Diseases

Research Journal of Infectious Diseases

ISSN 2052-5958
Original Research

Differential systemic MyD88-dependent versus MyD88- independent cytokine ratio by etiologic agent in adults with severe community-acquired pneumonia

Dean Campbell and Mark J. Cowan*

*Correspondence: Mark J. Cowan

Author Affiliations

Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Maryland School of Medicine, Baltimore, USA.


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 MyD88- dependent pathway to stimulate IL-8 and TNF-α production. TLR4 can also signal through a MyD88- independent 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.

Keywords: Pneumonia, cytokines, tumor necrosis factor-alpha, interferon-beta, interleukin-8, gramnegative, gram-positive, innate immunity

ISSN 2052-5958
Volume 2
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