| The effects of aminophylline on the superoxide anion generation of neutrophils from established human sepsis caused by acute pneumonia. |
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Yong Hoon Kim, Jun Young Park, Mi Kyong Cha, Sang Moo Lee, Hyeon Tae Kim, Soo Taek Uh, Yeon Tae Chung, Choon Sik Park |
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Department of Internal Medicine, College of Medicine, Soonchunhyang, University, Chonan, Seoul, Korea |
| 급성 폐렴에 의한 패혈증 환자에서 Aminophy lline 이 혈중 호중구의 과산화물 음이온 유리에 미치는 영향 |
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| Abstract |
Background
The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion , hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments.
Methods
We measured the 02 generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of 02 , was measured at a discrete time point (60 min) by the reduction of ferricytochrome c. PMA (10 μg/ ml) was used as a stimulating agent. PMNs were isolated at a concentration of 2 x 10 6 cells/ ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia
Results
The mean serum concentration of AMPH at 60 minutes was 8.8土 0.6 μg / m l. Sixty minutes after AMPH infusion the generation of 02 , was decreased from 0.076土 0.034 to 0.013土 0.004 (OD) (p< 0.05) and from 0.177土0.044 to 0.095 土 0.042 (OD) (p< 0.01) in the resting and stimulated PMNs respectively. Pa02 was not changed after AMPH infusion.
Conclusion
AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving Pa02 in the acute pneumonia. |
| Key Words:
Aminophylline, Superoxide Anion, Sepsis, Pneumonia, Cyclic AMP |
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