Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses.

Abstract

BACKGROUND: Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. HYPOTHESES: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. ANIMALS: Thirty-two healthy horses. METHODS: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1&#x2009;hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro-inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI. RESULTS: There was no effect of drug on clinical signs or pro-inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 &#xb1; 1.02 K/&#x3bc;l) compared to other groups (8.99 &#xb1; 0.94 K/&#x3bc;L; P&#x2009;<&#x2009;.009). Adminstration of HC was associated with higher blood neutrophil counts 12 hours after LPS infusion (10.40 &#xb1; 0.75 K/&#x3bc;l) compared to other groups (6.88 &#xb1; 0.68 K/&#x3bc;l; P < .001). Serum cortisol increased from 5.11 &#xb1; 1.48 &#x3bc;g/dL before LPS administration to 9.59 &#xb1; 1.83 &#x3bc;g/dL 1 h after completion of LPS infusion (T1) without an effect of treatment (P = 0.59). CONCLUSIONS AND CLINICAL IMPORTANCE: Ascorbic acid and HC appeared to protect against LPS-induced neutrophil depletion and could be considered as adjunctive therapy in horses with endotoxemia.