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Published ahead of print on October 3, 2002, doi:10.1164/rccm.200203-177OC

Am. J. Respir. Crit. Care Med., Volume 166, Number 12, December 2002, 1572-1578

A more recent version of this article appeared on December 15, 2002
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Submitted on March 5, 2002
Accepted on September 30, 2002

Strenuous resistive breathing induces plasma cytokines: role of antioxidants and monocytes

Theodoros Vassilakopoulos1*, Paraskevi Katsaounou2, Maria-Helena Karantza2, Androniki Kollintza2, Spyros Zakynthinos2, and Charis Roussos2

1 Critical Care and Pulmonary Services, National and Kapodistrian University, Athens, Attiki, Greece; Critical Care and Pulmonary Services, National and Kapodistrian University, Athens, Attiki, Greece, 2 Critical Care and Pulmonary Services, National and Kapodistrian University, Athens, Attiki, Greece

* To whom correspondence should be addressed. E-mail: tvassilakopoulos{at}yahoo.com.

Inspiratory resistive breathing increases plasma cytokines, yet the stimulus(i) and source (s) remain unknown. We tested the role of reactive oxygen species as stimuli and of monocytes as sources of resistive breathing-induced cytokines. Six healthy subjects performed two resistive breathing sessions at 75% of maximum inspiratory pressure before and after a combination of antioxidants (Vitamins E 200mg, A 50000 IU and C 1000mg per day for 60 days, allopurinol 600mg/day for 15 days and N-acetylcysteine 2 g/day for 3 days before the second session). Blood was drawn before, at the end, and at 30 and 120 minutes after resistive breathing. Before antioxidants, plasma cytokine levels (determined by ELISA) increased secondary to resistive breathing (TNF{alpha} and IL-6 by two-fold, IL-1ß by three-fold). After antioxidants plasma IL-1ß became undetectable, the TNF-{alpha} response to resistive breathing was abolished, and the IL-6 response was significantly blunted. Intracellular cytokine detection (by flow cytometry) showed no change in either the percentage of monocytes producing the cytokines or in their mean fluorescence intensity both before and after antioxidants. We conclude that oxidative stress is a major stimulus for the resistive breathing-induced cytokine production and that monocytes play no role in this process.
Key words: interleukin, flow cytometry, oxidative stress, inspiratory resistance, blood mononuclear cells.




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