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In vivo modulation of human neutrophil function by pentoxifylline in patients with septic syndrome
C Oismüller1, N Mayer, M Micksche
1Department of Anesthesiology and General Intensive Care, Sepsis Research Group, University of Vienna, Austria.
Abstract:
The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) was studied in 23 patients fulfilling the established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was administered (5 mg/kg) by intravenous infusion in 13 septic patients over a period of 180 min. The control group consisted of 10 patients with septic syndrome who received an infusion of physiological saline. For determination of RBA, 10 mL of blood was drawn at respective time intervals before, during, and after treatment with PTX or a placebo. RBA measurements were performed using a chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan, respectively. RBA measurements of each patient were performed in replicate samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15 min etc). RBA of PMN of septic patients was compared with RBA of PMN of healthy donors and patients receiving PTX were compared with controls. Our results demonstrate that PMN of patients with sepsis had an increased oxidative response compared with healthy donors. We found that PTX administered intravenously was able to reduce this reactivity. RBA was significantly decreased during PTX infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate, compared with the control group. No significant decrease was observed when PMN were stimulated with opsonized zymosan. These data suggest that PTX may be a valuable drug in septic state.
Insights
Pentoxifylline (PTX) reduces heightened polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) in sepsis patients. This finding suggests PTX may be a valuable therapeutic agent for managing sepsis by modulating immune cell responses.
Area of Science:
- Immunology
- Pharmacology
Background:
- Sepsis is characterized by an overactive immune response, including heightened polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA).
- This exaggerated oxidative response in sepsis can contribute to tissue damage.
Purpose of the Study:
- To investigate the effect of pentoxifylline (PTX) on PMN RBA in patients with sepsis.
- To determine if PTX can modulate the hyperactive immune response associated with sepsis.
Main Methods:
- A chemiluminescence assay was used to measure PMN RBA in 23 sepsis patients and 10 healthy donors.
- PTX was administered intravenously to 13 septic patients, with a control group receiving saline.
- RBA was measured before, during, and after treatment, with PMN stimulated by FMLP, PMA, and opsonized zymosan.
Main Results:
- PMN from septic patients exhibited significantly increased RBA compared to healthy donors.
- Intravenous PTX administration significantly reduced PMN RBA when stimulated by FMLP and PMA.
- No significant reduction in RBA was observed when PMN were stimulated with opsonized zymosan.
Conclusions:
- Pentoxifylline effectively attenuates the heightened oxidative response of PMN in sepsis patients.
- PTX demonstrates potential as a therapeutic agent to mitigate immune dysregulation in sepsis.