Effects of benzodiazepines on immunodeficiency and resistance in mice

Galdiero, F; Bentivoglio, C.; Nuzzo, I.; Ianniello, R; Capasso, Ciro; Mattera, Silvana; C, Nazzaro; Galdiero, Marilena; Carratelli, Caterina Romano

doi:10.1016/0024-3205(95)02199-0

Cited by 39 publications

(31 citation statements)

References 23 publications

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“…Previous reports showed that BDZs influence the immune system [19], especially the innate immune system [11]. Complex immune alterations occur following burn injury including immunosuppression with a concomitant hyperinflammatory response and both the innate and adaptive immune systems are involved [3].…”

Section: Discussionmentioning

confidence: 99%

The Burn Wound Inflammatory Response Is Influenced by Midazolam

et al. 2011

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Burn patients requiring hospitalization are often treated for anxiety with benzodiazepines (BDZs). Benzodiazepines are reported to influence immune system function. Immune system alterations are a major cause of burn-induced mortality. We wanted to determine whether the BDZ, midazolam given daily at an anxiolytic dose, had any influence on the burn injury-induced inflammatory response in the blood and wound. Mice received a 15% total body surface area flame burn and received either midazolam 1 mg/kg i.p. or saline 0.1 ml daily. Blood and skin wounds were harvested 24 h after injection on post-burn day 2, 3, 7, or 8. Mice treated with midazolam had significantly lower serum IL-1β (p=0.002), TNF-α (p=0.002), IL-6 (p=0.016), IL-10 (p=0.009), and TGF-β (p=0.004) than saline-treated mice, with little impact on serum chemokine levels. In the wound, TNF-α and IL-10 were the only cytokines significantly influenced by the drug, being lower (p=0.018) and higher (p=0.006), respectively. The chemokines in the wound influenced significantly by midazolam were MIP-1α, MIP-1β, and MIP-2 while MCP-1 and KC were not. There were more inflammatory cells at the burn wound margin in midazolam-treated mice on post-burn day 3. Although serum nitrate/nitrite was significantly increased by midazolam (p=0.03), both eNOS and iNOS mRNA expression in the wound were similar to the saline group. We found that midazolam given daily after burn injury significantly influenced the inflammatory response. The clinical implications of these findings on wound healing and shock following burn injury, especially larger burns, deserve further investigation.

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Section: Discussionmentioning

confidence: 99%

The Burn Wound Inflammatory Response Is Influenced by Midazolam

et al. 2011

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“…Previous studies have shown that BDZs attenuate the proinflammatory response in vivo, 9,16,17 which led us to investigate what impact midazolam treatment for 8 days would have had on the survival rate after the Figure 4. Survival rates in sham mice.…”

Section: Influence Of Midazolam On Lps-induced Septic Shockmentioning

confidence: 99%

Mice Treated With a Benzodiazepine Had an Improved Survival Rate Following Pseudomonas aeruginosa Infection

Dugan¹,

Gregerson²,

Neely³

et al. 2010

Journal of Burn Care & Research

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Psychological stress has a high incidence after burn injury, therefore, anxiolytic drugs are often prescribed. Unfortunately, to date, no burn study has investigated the effects of anxiolytic drugs on the ability to fight infection. This study was undertaken to determine if psychological stress, anxiety-modulating drugs, or both, alter survival following an infection. On day 0, 7-week-old male C57Bl/6 mice either received a 15% full-thickness flame burn or were sham treated (anesthesia and shaved), whereas controls received no treatment. Mice received midazolam (1 mg/kg intraperitoneally) or saline daily and were stressed by exposure to rat in a guinea pig cage or placed in an empty cage for 1 hour a day, beginning on postburn day 1. For the survival experiments, mice either received bacteria after 2 or 8 consecutive days of predator exposure and drug treatment, which continued daily for 7 days after inoculation. In a separate set of experiments, after eight daily injections of midazolam, mice were given lipopolysaccharide, bacteria, or saline and were killed 12 hours later. Mice that received midazolam had improved survival rates when compared with their saline-treated counterparts, and the protective effect was more significant the more days they received the drug. For most of the cytokines, the bacteria-induced increase was significantly attenuated by midazolam as was the amount of bacteria in the liver. The protective effect seems to be independent of the drug's anxiolytic activity as there were no significant differences in survival between the predator-stressed and the nonstressed mice. The mechanisms responsible for the protective effect remain to be elucidated.

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“…23,24 A 1995 study found that bacteremic mice treated with diazepam for 2-3 months had higher mortality and reduced neutrophil chemotaxis and phagocytosis compared with mice not treated with benzodiazepines. 25 In a separate study, exposing murine dendritic cells to midazolam for 24 hours and then stimulating them with lipopolysaccharide (LPS) inhibited their maturation and capacity to stimulate helper T-cells. 26 Similar findings have been reported in human studies using midazolam: one study of patients taking midazolam for migraine reported decreased neutrophil chemotaxis and phagocytosis 27 ; another study of patients who received midazolam during surgery documented decreases in serum IL-1B, IL-6, IL-8, and TNF-α levels.…”

Section: Sedation and Immune Function: Basic Science Studiesmentioning

confidence: 99%

The Relationship Between Sedatives, Sedative Strategy, and Healthcare-Associated Infection: A Systematic Review

Caroff

Szumita

2016

Infect. Control Hosp. Epidemiol.

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BACKGROUND Healthcare-associated infections (HAIs) cause significant morbidity in critically ill patients. An underappreciated but potentially modifiable risk factor for infection is sedation strategy. Recent trials suggest that choice of sedative agent, depth of sedation, and sedative management can influence HAI risk in mechanically ventilated patients. OBJECTIVE To better characterize the relationships between sedation strategies and infection. METHODS Systematic literature review. RESULTS We found 500 articles and accepted 70 for review. The 3 most common sedatives for mechanically ventilated patients (benzodiazepines, propofol, and dexmedetomidine) have different pharmacologic and immunomodulatory effects that may impact infection risk. Clinical data are limited but retrospective observational series have found associations between sedative use and pneumonia whereas prospective studies of sedative interruptions have reported possible decreases in bloodstream infections, pneumonia, and ventilator-associated events. CONCLUSION Infection rates appear to be highest with benzodiazepines, intermediate with propofol, and lowest with dexmedetomidine. More data are needed but studies thus far suggest that a better understanding of sedation practices and infection risk may help hospital epidemiologists and critical care practitioners find new ways to mitigate infection risk in critically ill patients. Infect Control Hosp Epidemiol 2016;1-9.

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Effects of benzodiazepines on immunodeficiency and resistance in mice

Cited by 39 publications

References 23 publications

The Burn Wound Inflammatory Response Is Influenced by Midazolam

The Burn Wound Inflammatory Response Is Influenced by Midazolam

Mice Treated With a Benzodiazepine Had an Improved Survival Rate Following Pseudomonas aeruginosa Infection

The Relationship Between Sedatives, Sedative Strategy, and Healthcare-Associated Infection: A Systematic Review

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