Age-associated changes to pathogen-associated molecular pattern-induced inflammatory mediator production in dogs

Objective To determine whether older dogs will have a more pronounced pro-inflammatory response and blunted anti-inflammatory response to pathogen-associated molecular patterns (PAMPs) compared with younger dogs. Design Prospective. Setting University teaching hospital. Animals Thirty-eight privately owned sexually altered dogs of various ages. Interventions Blood was collected for HCT, WBC count, plasma biochemical analysis, and whole blood culture. Whole blood was stimulated with lipopolysaccharide (LPS) or, lipoteichoic acid or, peptidoglycan or, addition of phosphate-buffered saline. Tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 production from whole blood were compared among young, middle aged, and geriatric dogs. Measurements and Main Results LPS, lipoteichoic acid, and peptidoglycan stimulated significant TNF, IL-6, and IL-10 production from canine whole blood compared with phosphate-buffered saline. Whole blood from geriatric dogs had a blunted IL-10 response to LPS stimulation and middle-aged dogs had increased LPS-induced TNF production compared with the other groups. Conclusion PAMPs from gram-positive and gram-negative bacteria stimulate TNF, IL-6, and IL-10 production from canine whole blood. The inflammatory mediator response to PAMPs from gram-negative bacteria alters with age and may be one factor contributing to mortality in geriatric dogs with sepsis.