Effect of pentoxifylline on changes in neutrophil sequestration and emigration in the lungs

Abstract

The response of neutrophils to inflammatory stimuli includes sequestration, adhesion, and migration. Pentoxifylline protects against many neutrophil-mediated lung injuries. This study investigated whether pentoxifylline prevented changes in neutrophil kinetics induced by infusion of complement fragments or neutrophil emigration induced by Streptococcus pneumoniae. Complement fragments were infused in New Zealand White rabbits treated with pentoxifylline or saline, and the circulating neutrophil counts in the arterial and venous blood samples were measured. Neutrophil emigration was induced by intrabronchial instillation of S. pneumoniae and quantitated morphometrically. The results show that, at doses achievable in vivo, pentoxifylline did not prevent either the CD18-dependent or -independent phase of complement-mediated neutrophil sequestration within the pulmonary microvasculature or the release of neutrophils from the bone marrow. Pentoxifylline also did not alter either the deformability of unstimulated leukocytes or stimulus-induced decreases in deformability. Finally, neutrophil emigration into the alveolar space was neither attenuated nor accentuated by pentoxifylline. These data suggest that, in vivo, pentoxifylline does not protect against lung injury by inhibiting neutrophil sequestration or emigration and may act to alter the generation of mediators that affect neutrophil behavior, rather than acting directly on neutrophils.

Role of the intercellular adhesion molecule-1(ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, anti-ICAM-1 monoclonal antibodies, and ICAM-1 mutant mice.

“…Neutrophil emigration into the alveolar spaces was quantitated on paraffin-embedded histologic sections using point-counting techniques to determine the percentage of the distal airspace that was occupied by neutrophils (31,32). 500 points were counted in each of five fields of alveolar space and alveolo-capillary walls on histologic sections at 200 magnification.…”

Sequential release of TNFα and phospholipase A2 in a rat model of LPS‐induced pleurisy

“…12 Other authors report that the ability of TNFa inhibitors to protect animals from ogogen-induced lung injury is not linked to a reduction in PMN sequestration. 16 In the light of this knowledge, it is not unexpected that the inhibition of TNFa alone did not affect leucocyte accumulation. Surprisingly, when we pretreated animals with the anti-TNFa antibody, we observed a strong increase in sPLA 2 levels in the cell-free pleural washing at 48 hours.…”

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation

“…Pentoxifylline may also inhibit the important interleukin, interleukin-1, and tumor necrosis factor, which are critical in the pathogenesis of ischemia-reperfusion injury. 10,11 Although pentoxifylline clearly improves and augments function in conjunction with low-pressure reperfusion by reducing neutrophil trapping in the lung and subsequent free radical release, any benefits attained through its combination with highpressure reperfusion remain to be seen.…”