Activated neutrophils are obviously playing role in the lung microvascular pathophysiology. The removal of neutrophils by filtration, by anti-neutrophil antibody, or by chemical agents such as nitrogen mustard is beneficial for the experimental ALI. Antiadhesion molecule antibodies are also beneficial . We have reported that the inhibition of L-selectin attenuated ovine ALI , but anti-P-selectin antibody did not. Since P-selectin is induced at very early time points and decreases soon after the peak expression, the inhibition of P-selectin could not be effective. In rat or mouse models, there are several papers showing the beneficial effects of E-selectin or ICAM-1 inhibition. However, in clinical trials in sepsis, none of these antiadhesion molecule studies were shown to be effective. The reason for this is not known. Perhaps the adhesion molecule-independent accumulation of neutrophils, such as increased cell stiffness, may be involving in sepsis-related ALI.
To inhibit neutrophil activation, there are several potent agents. Cepharanthine, an alkaloid extracted from an herbal plant, inhibits neutrophil activation and has been shown effective in ALI models in rats and sheep. It inhibits neu-trophil elastase release and oxygen radical production. Intracellular cyclic AMP (cAMP) is known to inhibit neu-trophil activation. The increase in neutrophil cAMP level inhibits F-actin activation, which results in the attenuation of deformability. Also, it inhibits neutrophil elastase release and superoxide production. Since cAMP is metabolized into 5'AMP by phosphodiesterase (PDE), PDE inhibitors increase the intracellular cAMP levels. Caffeine or amino-phylline are well-known PDE inhibitors and are effective in asthma attack because increased cAMP levels in bronchial smooth muscle cells attenuate the bronchial constriction and spasm. In addition to that, those PDE inhibitors may have a beneficial effect through their anti-inflammatory properties. The increase in cAMP levels in the microvascular endothe-lial cells attenuates the vascular leakage, so there is a possibility that PDE inhibitors also inhibit cast formation. Adenosine administration shows similar effects in various animal models, but again, we need to confirm this efficacy in clinical trials.
Was this article helpful?
Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.