The activity of Protectin DX, 17 HDHA and Leukotriene B4 is correlated with Interleukin-1beta (IL-1beta) and Interleukin-1 Receptor Antagonist (IL-1Ra) in the early subacute phase of stroke

Abstract

Ischemic stroke is a leading cause of mortality and disability in adults. The inflammatory cascade is driven by various inflammatory molecules, such as interleukin-1β (IL-1β), and counteracted by its antagonist, interleukin-1 receptor antagonist (IL-1Ra). Eicosanoids are inflammatory derivatives of free fatty acids. Arachidonic acid (AA) derivatives exhibit pro-inflammatory activity, while eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives, known as specialized pro-resolving mediators, have anti-inflammatory properties. This study aimed to analyze potential associations between eicosanoids and key inflammatory molecules, including IL-1β and its antagonist IL-1Ra. In this prospective study, we investigated inflammatory molecules in 73 ischemic stroke patients. We analyzed interactions between IL-1β, IL-1Ra, and eicosanoids as follows: resolvin E1, prostaglandin E2, resolvin D1, lipoxin A4 (5S, 6R, 15R), protectin DX, maresin 1, leukotriene B4, 18RS-HEPE, 13S-HODE, 9S-HODE, 15S-HETE, 17 HDHA, 12S-HETE, 5-oxo-ETE, and 5-HETE. In 73 ischemic stroke patients, mean IL-1β was 1.31 ± 1.54 pg/mL and IL-1Ra 810.8 ± 691.0 pg/mL. Spearman correlations showed positive associations between IL-1β and protectin DX (ρ = 0.56, p < 0.001), and 17 HDHA (ρ = 0.26, p < 0.05) and 5-oxo-ETE (ρ = 0.27, p < 0.05). IL-1Ra correlated negatively with protectin DX (ρ = −0.58, p < 0.001) and 17 HDHA (ρ = −0.29, p < 0.05), and positively with leukotriene B4 (ρ = 0.34, p < 0.005). After multivariable adjustment, associations with IL-1β lost statistical significance, whereas the inverse relationships between IL-1Ra and protectin DX/17 HDHA remained significant (p < 0.005). Despite the known anti-inflammatory roles of protectin DX and 17 HDHA, and the pro-inflammatory role of leukotriene B4, their activity in the early subacute phase of ischemic stroke appears to be influenced by complex interplays, possibly mediated by IL-1β and IL-1Ra. The activity of protectin DX, 17 HDHA, and leukotriene B4 is correlated with IL-1β and IL-1Ra levels in the early subacute phase of stroke.