Presentations

Abstract

Introduction: Increased inflammatory cytokines and biomarkers have been related to the degradation of the blood brain barrier. The fragility of this barrier can result in an increasing number of proteins that can enter the central nervous system circulation, which has been postulated to cause brain dysfunction like delirium. GM-CSF, granulocyte-macrophage colony stimulating factor, and MCP-1, monocyte chemoattractant protein 1, both stimulate macrophages/monocytes, specifically M1 pro-inflammatory macrophages. Medications like propofol and dexmedetomidine have been shown to mitigate inflammation by downregulating the polarization of M1 macrophages and instead upregulating M2 macrophages. M2 macrophages produce anti-inflammatory cytokines like IL-13. Anti-inflammatory cytokines attenuate inflammation and thus have a protective effect on the brain. Dexmedetomidine has been shown to cause greater attenuation of inflammation than propofol in mouse models.

Methods: The samples that were analyzed were from a double-blind, randomized, controlled trial conducted at 13 different medical centers. The population of this trial includes adults who were sequentially admitted to a medical or surgical ICU, with suspected or known infection, and were treated with continuous sedation for invasive mechanical ventilation. The medication used for sedation was either dexmedetomidine (5 μg per milliliter) or propofol (10 mg per milliliter). The samples from this trial were then sent for analysis to calculate the biomarker levels per sample.

Results: Prior research has shown that there is a significant difference in biomarker levels during states of inflammation. IL-13 was increased as a compensatory mechanism to downregulate inflammation from insulin resistance. Similarly, MCP-1 was increased in a critical limb ischemia state of inflammation. GM-CSF was significantly increased to more than 4 times the physiological level during an infectious inflammatory state. The significant difference between the physiologic and inflammatory states highlights how GM-CSF is increased in inflammation. For the pending samples, it is predicted that MCP-1 and GM-CSF will both be significantly increased in the patients in an inflammatory state. However, based on the prior research, it is unclear whether IL-13 will be significantly increased.

Conclusion: Analyzing the inflammation pathway can help determine how acute brain dysfunction and delirium develops. The confirmation of this correlation can provide mechanistic pathways to attenuate the inflammatory response to help reduce the risk for brain disease. Should one medication prove to be more efficient in attenuating the inflammatory response, further prospective work on implications among high-risk participants can be formulated to study. This can encourage further research into regulating the inflammatory response to protect the brain from developing acute dysfunction, including delirium.