Ensemble Analysis Identifies Nasal 15-Keto-Pge(2) As A Predictor Of Recovery In Experimental Rhinovirus Colds

Background. Symptom intensity during a common cold is highly variable, particularly after the illness peaks, contributing to delay in recovery. Rhinoviruses frequently cause colds and, during acute infections, generate leukotriene B-4 and prostaglandin E-2 (PGE(2)). PGE(2) is known to initiate oxylipin class switching and resolution of acute inflammation. Thus, we hypothesized that during acute rhinovirus colds, oxylipins with pro-resolving capabilities reduce symptom severity and speed recovery.Methods. Four groups of healthy volunteers were inoculated with placebo or 3 different doses of rhinovirus A16. Participants kept daily records of symptoms and contributed serial nasal lavage fluid samples. We collected semi-quantitative mass spectrometry data for 71 oxylipins in these acute samples from all participants. An ensemble analysis approach was used to further reduce this dataset.Results. Levels of 15-keto-PGE 2 at day 3 of the cold were consistently among the top candidates in these models of recovery symptoms. 15-keto-PGE(2) was the only oxylipin with an interaction between inoculum dose and time. Acute 15-keto-PGE(2) levels were inversely associated with symptoms during cold recovery in a multivariable analysis (P = .0043).Conclusions. These findings show that high 15-keto-PGE(2) levels during the acute cold are associated with fewer symptoms during recovery.