Hydroxychloroquine Mitigates Cytokine Storm and Prevents Critical Illness Neuromyopathy in a Rat Sepsis Model

Abstract

Background and Objectives: It is known that critical illness and associated neuromuscular problems begin to appear in patients hospitalized in the intensive care unit (ICU) for more than a week. The goal of this study was to research the role of hydroxychloroquine (HCQ) in the treatment of cytokine storm and critical illness neuromyopathy (CINM) in a rat sepsis model. Materials and Methods: Rats were assigned into three groups, and a feces intraperitoneal-injection group (FIP) procedure was carried out on 30 rats to induce a model of sepsis for critical illness polyneuromyopathy (CINM). The study groups were as follows: Group 1: control (nonoperative and orally fed control, n = 10), Group 2: FIP with 0.9% NaCl saline was given as 1 mL/kg/day by oral gavage (n = 10), and Group 3: FIP with 10 mg/kg/day of hydroxychloroquine (Plaquenil 200 mg) administered by oral gavage (n = 10). Electrophysiological recordings (EMG) were conducted six days after surgery. EMG was carried out three times on the right sciatic nerve, which was stimulated with supramaximal intensity utilizing a bipolar needle electrode at the sciatic notch. Tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), lactic acid levels, and interleukin-6 (IL-6) were evaluated. Results: In terms of TNF-α, MDA, lactic acid levels, and IL-6, there was a statistically significant decrease in the CINM + 10 mg/kg HCQ group compared to the CINM and saline group (p < 0.0001, p < 0.05, p < 0.05, and p < 0.05, respectively). Compound muscle action potentials (CMAPs) latency and duration were decreased in the CINM + 10 mg/kg HCQ group compared to other groups (p < 0.01 and p < 0.001). However, CMAP amplitude was significantly higher in the CINM + 10 mg/kg HCQ group unlike the CINM and saline group (p < 0.001). Conclusions: This is the first study to demonstrate the effects of HCQ on CINM in a rat model of sepsis. The findings of our research suggest that hydroxychloroquine may be used as a potential therapeutic agent in the treatment of sepsis. Hydroxychloroquine may have an important effect in the pathogenesis of sepsis-associated CINM by reducing cytokine production and oxidative stress.

Keywords: critical illness neuromyopathy; hydroxychloroquine; interleukin-6; malondialdehyde; muscle action potential; tumor necrosis factor-alpha.

Figure 1

Electrophysiological recordings or electromyography (EMG) measurements.

Figure 2

Samples of compound muscle action potential (CMAP) recorded from (a) normal group, (b) feces intraperitoneal-injection (FIP) and saline group, and (c) FIP and 10 mg/kg hydroxychloroquine group.