Effects of pentoxifylline on in vivo leukocyte function and clearance of group B streptococci from preterm rabbit lungs.
OBJECTIVE
Pentoxifylline was evaluated for its ability to enhance inactivation of group B streptococci in lungs of prematurely born rabbits. Mechanisms associated with intrapulmonary streptococcal clearance and the pharmacodynamics of pentoxifylline were also investigated.


METHODS
Randomized, controlled animal trial.


METHODS
University research laboratory.


METHODS
A total of 123 New Zealand rabbits were delivered prematurely by cesarean section and were used for clearance studies. Twenty-three preterm pups were additionally utilized to study the pharmacodynamics of pentoxifylline.


METHODS
Preterm rabbits were infected with group B streptococcal aerosols and given intraperitoneal injections of either pentoxifylline (25, 12.5, and 12.5 mg/kg) or placebo at 0, 6, and 12 hrs after infection.


RESULTS
At 0, 4, and 24 hrs, the numbers of streptococci were determined in the left lung, while the right lung underwent bronchoalveolar lavage to quantify intra-alveolar leukocytes, phagocytosis of inhaled bacteria, and concentrations of lysozyme and tumor necrosis factor. In a separate experiment, blood and bronchoalveolar fluid from infected animals were analyzed for pentoxifylline content. Streptococcal proliferation was less in pentoxifylline-treated animals than in controls at 24 hrs (p < .01). Pulmonary macrophages and polymorphonuclear leukocytes recovered from bronchoalveolar lavage fluid did not differ in numbers or phagocytic activity. Pentoxifylline-treated animals had lower levels of lysozyme (p < .02) and tumor necrosis factor (p < .005) in bronchoalveolar lavage fluid compared with placebo-treated pups. Therapeutic levels of pentoxifylline were achieved in blood and bronchoalveolar lavage fluid.


CONCLUSIONS
Despite lowering lysozyme and tumor necrosis factor content in epithelial lining fluid, pentoxifylline improves the inactivation of group B streptococci in preterm rabbit lungs. These findings suggest that increased group B streptococcal clearance was coincident with an anti-inflammatory effect due to pentoxifylline. We conclude pentoxifylline may be clinically useful as an adjunctive therapy for group B streptococcal pneumonia in newborns.
Mah
M P
MP
Department of Pediatrics, School of Medicine, University of California, Los Angeles.
Aeberhard
E E
EE
Gilliam
M B
MB
Sherman
M P
MP
D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005333:Fetus; D007958:Leukocyte Count; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009113:Muramidase / Q000032:analysis; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D010431:Pentoxifylline / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D010587:Phagocytosis / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000473:pathology; D013292:Streptococcus agalactiae; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
D014409:Tumor Necrosis Factor-alpha; D009113:Muramidase; D010431:Pentoxifylline