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Design of Cecal Ligation and Puncture and Intranasal Infection Dual Model of Sepsis-Induced Immunosuppression
Published on: June 15, 2019
Dopamine affects cellular immune functions during polymicrobial sepsis
Reiner Oberbeck1, Daniel Schmitz, Klaus Wilsenack
1Department of Trauma Surgery, University Hospital of Essen, Hufelandstrasse 55, 45122, Essen, Germany. reineroberbeck@hotmail.com
Objective:
To determine whether infusion of dopamine modulates cellular immune functions and survival during systemic inflammation.
Design And Setting:
Randomized animal study, university research laboratory, Level I trauma center.
Subjects:
Male NMRI mice.
Interventions:
Mice were subjected to laparotomy (sham intervention, LAP) or polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice in each of these conditions received either an intraperitoneal infusion of 0.9% saline (CLP/saline; LAP/saline) or an intraperitoneal infusion of dopamine (1.0 microg/kg/min i.p., CLP/DOP; LAP/DOP). Metabolic data and survival were monitored 24 h and 48 h after onset of sepsis, and animals were terminated 48 h after induction of sepsis to determine splenocyte apoptosis (Annexin V binding capacity), splenocyte proliferation (3H-Thymidine incorporation assay), splenocyte IL-2, IL-6 and IFN-gamma release (ELISA) and leukocyte distribution (WBC; CD3, CD4, CD8, B220, F4/80, NK1.1).
Measurements And Results:
Infusion of dopamine in septic mice increased splenocyte apoptosis and decreased splenocyte proliferation and IL-2 release of septic mice. Furthermore, an inhibitory effect of dopamine infusion on splenocyte proliferation and the release of the TH1-cytokines IL-2 and IFN-gamma was observed in sham operated control mice. These effects were paralleled by a decreased survival of dopamine-treated septic animals (47% vs. 67%). Treatment with DOP did not affect sepsis-induced changes of leukocyte distribution.
Conclusions:
We conclude that dopamine is capable of modulating cellular immune functions in a murine model of sepsis.
Insights
Dopamine infusion in septic mice increased immune cell death and decreased proliferation, reducing survival. This study shows dopamine modulates cellular immune functions during systemic inflammation in mice.
Area of Science:
- Immunology
- Pharmacology
- Critical Care Medicine
Background:
- Systemic inflammation, such as sepsis, profoundly impacts immune cell function.
- Understanding modulators of immune response during sepsis is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the effect of dopamine infusion on cellular immune responses and survival in a murine model of sepsis.
- To determine if dopamine administration alters splenocyte apoptosis, proliferation, cytokine release, and leukocyte distribution.
Main Methods:
- A randomized animal study was conducted using male NMRI mice subjected to cecal ligation and puncture (CLP) to induce sepsis or sham laparotomy (LAP).
- Mice received intraperitoneal infusions of either saline or dopamine (1.0 microg/kg/min).
- Immune cell functions (apoptosis, proliferation, cytokine release) and survival were assessed 24 and 48 hours post-induction.
Main Results:
- Dopamine infusion in septic mice led to increased splenocyte apoptosis and decreased splenocyte proliferation and IL-2 release.
- Septic mice treated with dopamine exhibited reduced survival rates (47% vs. 67% in saline-treated controls).
- Dopamine also inhibited splenocyte proliferation and TH1-cytokine release (IL-2, IFN-gamma) in non-septic (sham) mice.
Conclusions:
- Dopamine administration significantly modulates cellular immune functions in a murine model of sepsis.
- The findings suggest that dopamine may have detrimental effects on immune response and survival during systemic inflammation.
- Further research is warranted to elucidate the precise mechanisms and clinical implications of dopamine's immunomodulatory effects.
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