IL-1Rahigh-IL-4low-IL-13low: A Novel Plasma Cytokine Signature Associated with Olfactory Dysfunction in Older US Adults

Abstract

Inflammation has been implicated in physical frailty, but its role in sensory impairment is unclear. Given that olfactory impairment predicts dementia and mortality, determining the role of the immune system in olfactory dysfunction would provide insights mechanisms of neurosensory decline. We analyzed data from the National Social Life, Health and Aging Project, a representative sample of home-dwelling older US adults. Plasma levels of 18 cytokines were measured using standard protocols (Luminex xMAP). Olfactory function was assessed with validated tools (n-butanol sensitivity and odor identification, each via Sniffin’ Sticks). We tested the association between cytokine profiles and olfactory function using multivariate ordinal logistic regression, adjusting for age, gender, race/ethnicity, education level, cognitive function, smoking status, and comorbidity. Older adults with the IL-1Rahigh-IL-4low-IL-13low cytokine profile had worse n-butanol odor sensitivity (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19–2.17) and worse odor identification (OR = 1.42, 95% CI 1.11–1.80). Proinflammatory, Th1, or Th2 cytokine profiles were not associated with olfactory function. Moreover, accounting for physical frailty did not alter the main findings. In conclusion, we identified a plasma cytokine signature—IL-1Rahigh-IL-4low-IL-13low—that is associated with olfactory dysfunction in older US adults. These data implicate systemic inflammation in age-related olfactory dysfunction and support a role for immune mechanisms in this process, a concept that warrants additional scrutiny.

International consensus statement on allergy and rhinology: Olfaction

“…1432 They reported the presence of EOG responses and functionally mature OSNs at the insertion level of the middle turbinate. Some EOG work also suggested the existence of a specific topographical distribution of ORs with some recording sites only responding to certain odors, 1426 and that the EOG was odorant specific 1427 (and even specific for odorous enantiomers 1433 ). Areas that responded maximally to a pleasant odorant were also likely to respond strongly to other pleasant odorants, and a location that responded maximally to an unpleasant odorant was likely to respond strongly to other unpleasant odorants.…”

“…179,180,183,1264 Four studies have evaluated inflammatory proteins in non-CRS-related OD. 181,[1265][1266][1267] Schubert et al 1266 found no associations between baseline systemic Creactive protein, IL-6, and TNF-α to subsequent development of OD over 10 years and Darnell et al 1265 found a systemic cytokine profile associated with frailty (high IL-1 receptor antagonist, low IL-4, low IL-13) had significantly higher odds of worse olfaction. Henkin et al 181 found that IL-6 levels were significantly higher in the plasma, saliva, and nasal mucus of hyposmic patients compared with normosmic patients.…”