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Pentoxifylline enhancement of defective neutrophil function and host defense in neonatal mice
P J Krause1, J Kristie, W P Wang
1Department of Pediatrics, Hartford Hospital, Connecticut.
Abstract:
Decreased neutrophil (PMN) chemotaxis is thought to contribute to the increased morbidity and mortality from infection in newborn infants. Pentoxifylline, a methylxanthine, has previously been shown to augment PMN chemotaxis in vitro. The authors therefore investigated the effects of pentoxifylline on 1) in vitro PMN chemotaxis, 2) in vivo leukocyte accumulation, and 3) protection against Staphylococcus aureus infection in newborn mice. Using a modified Boyden chamber system, they demonstrated that pentoxifylline significantly enhanced neonatal PMN chemotaxis in a dose-dependent manner. Additionally, pentoxifylline was found to increase PMN accumulation in vivo in a proteose peptone-induced peritonitis model. Finally, the survival rate in experimentally induced S aureus infection was 51% in neonatal mice given pentoxifylline, compared with 17% in a control (nonpentoxifylline) group (P less than 0.01). These data demonstrate pentoxifylline modulation of PMN migration and enhancement of host defense against bacterial infection.
Insights
Pentoxifylline enhances neutrophil (PMN) chemotaxis and boosts the immune response in newborn mice. This methylxanthine treatment significantly improves survival rates against Staphylococcus aureus infections.
Area of Science:
- Immunology
- Neonatal Medicine
- Pharmacology
Background:
- Decreased neutrophil (PMN) chemotaxis is linked to increased infection-related morbidity and mortality in newborns.
- Pentoxifylline, a methylxanthine, has demonstrated in vitro potential to augment PMN chemotaxis.
Purpose of the Study:
- To investigate the effects of pentoxifylline on neonatal neutrophil function and host defense.
- To evaluate pentoxifylline's impact on in vitro PMN chemotaxis, in vivo leukocyte accumulation, and protection against Staphylococcus aureus infection in newborn mice.
Main Methods:
- Utilized a modified Boyden chamber system to assess in vitro PMN chemotaxis.
- Employed a proteose peptone-induced peritonitis model to evaluate in vivo leukocyte accumulation.
- Assessed survival rates in neonatal mice experimentally infected with Staphylococcus aureus.
Main Results:
- Pentoxifylline significantly enhanced neonatal PMN chemotaxis in a dose-dependent manner.
- Pentoxifylline increased PMN accumulation in vivo.
- Neonatal mice treated with pentoxifylline exhibited a significantly higher survival rate (51%) against S. aureus infection compared to controls (17%).
Conclusions:
- Pentoxifylline effectively modulates PMN migration in neonatal models.
- Pentoxifylline enhances host defense mechanisms against bacterial infections in newborns.
- Pentoxifylline shows promise as a therapeutic agent to combat infections in neonates.