Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

Abstract

The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

Ethanol Consumption and Sepsis: Mechanisms of Organ Damage

“…Sepsis may increase the levels of IL-6 and TNF-α [4,15], damaging different organs [5,26] culminating in septic shock [22]. Increased levels of blood urea nitrogen and creatinine may occur during sepsis, important markers of kidney damage [4].…”

“…Increased levels of blood urea nitrogen and creatinine may occur during sepsis, important markers of kidney damage [4]. Ethanol may also contribute to high creatinine and urea levels [15], leading to kidney damage and acute tubular necrosis [5]. Up to 50% of patients develop acute kidney injury in sepsis [1,5].…”

“…The ways in which ethanol can aggravate sepsis are not fully elucidated. Ethanol consumption directly affects immune function, leading to a decrease in the lymphocytic response, as well as alteration in cytokine production by lymphocytes and macrophages [15]. Other studies have demonstrated that the administration of ethanol suppresses the elimination of bacteria present in sepsis, with decreased pro-inflammatory chemokine levels (TNF-α and IL-6) [1,4,26].…”

“…Ethanol can modulate the antioxidant system, leading to increased production of reactive oxygen species (ROS) [2]. The extent of the effects caused by ethanol is influenced by factors such as consumption pattern, quantity ingested, gender and organ system affected [15]. Chronic consumption of ethanol is directly related to susceptibility to infections due to direct toxic effects on the immune system [4,16,17].…”

“…During sepsis, an increase in the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) [4,15], and decrease in CD4 + and CD8 + lymphocytes [6] was observed. There is an induction of intestinal epithelial apoptosis, which favors an increase in the permeability of the intestine, thus causing an increase in the systemic inflammatory process, since the intestine is closely linked to the immune system [6].…”