Amitriptyline Usage Exacerbates the Immune Suppression Following Burn Injury

Abstract

Currently, over 10% of the US population is taking antidepressants. Numerous antidepressants such as amitriptyline are known to inhibit acid sphingomyelinase (Asm), an enzyme that is known to mediate leukocyte function and homeostasis. Severe burn injury can lead to an immunosuppressive state that is characterized by decreased leukocyte function and numbers as well as increased susceptibility to infection. Based upon the intersection of these facts, we hypothesized that amitriptyline-treated, scald-injured mice would have an altered immune response to injury as compared with untreated scald mice. Prior to burn, mice were pretreated with amitriptyline. Drug- or saline-treated mice were subjected full thickness dorsal scald- or sham-injury. Immune cells from spleen, thymus, and bone marrow were subsequently harvested and characterized. We first observed that amitriptyline prior to burn injury increased body mass loss and spleen contraction. Both amitriptylinetreatment and burn injury resulted in a 40% decrease of leukocyte Asm activity. Following scald injury, we demonstrate increased reduction of lymphocyte precursors in the bone marrow and thymus, as well as mature leukocytes in the spleen in mice that were treated with amitriptyline. We also demonstrate that amitriptyline treatment prior to injury reduced neutrophil accumulation following peptidoglycan stimulus in scald-injured mice. These data show that Asm alterations can play a significant role in mediating alterations to the immune system after injury. The data further suggest that those taking antidepressants may be at a higher risk for complications following burn injury.

Bronchoalveolar Lavage Microvesicles Protect Burn-Injured Mice from Pulmonary Infection

“…This is thought to be related to the systemic immunosuppressed state following injury 28–30 . However, the mechanism of increased susceptibility to PA remains unclear.…”

What's New in Shock, November 2016?

“…Returning to the investigation of burn injury, Dr. Caldwell’s laboratory has revealed another important aspect to the treatment of depression (15). Although depression is not considered normally in the area of shock research, depression and medication for its treatment are fairly prevalent in the United States.…”

“…Although depression is not considered normally in the area of shock research, depression and medication for its treatment are fairly prevalent in the United States. Dr. Johnson, et al were able to determine that amitriptyline, a tricyclic antidepressant that inhibits acid sphingomyelinase, had significant effects on the immunity of host after burn injury (15). This included a reduction in lymphocyte precursors, lymphocyte numbers and neutrophil recruitment (15).…”

“…Dr. Johnson, et al were able to determine that amitriptyline, a tricyclic antidepressant that inhibits acid sphingomyelinase, had significant effects on the immunity of host after burn injury (15). This included a reduction in lymphocyte precursors, lymphocyte numbers and neutrophil recruitment (15). Clearly, their work suggests that future precision medicine for inflammation, injury and infection will require consideration of the patient’s ‘medication profile.’…”

Influence of Haes-Lx-5% Infusion Solution on the Dna Content of Endocrine Glands Cells Against the Background of Thermal Burn of Skin in Rats

“…Histological, immunological and biochemical manifestations of adenohypophysis [2], adrenal glands [10,18] and thymus [13,28] damages have been established at different times in the course of burn disease, which lead to severe organ damage [23,22]. However, the molecular mechanisms of these disorders remain poorly understood, which makes it difficult to develop pathogenetic treatments for burn disease.…”