Journal
PULMONARY PHARMACOLOGY & THERAPEUTICS
Volume 17, Issue 5, Pages 281-287Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2004.06.002
Keywords
1,8-cineol (eucalyptol); secretolysis; COM; asthma; sinusitis
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Background: The therapeutic value of secretolytic agents in COPI) and asthma is still disputed. For this reason, in a preclinical study we aimed to test the potential anti-inflammatory efficacy of 1,8-cineol (eucalyptol) in inhibiting polyclonal stimulated cytokine production by human unselected lymphocytes and LPS-stimulated monocytes. Methods: Cytokine production was determined following 20 It of incubation cells with 1,8-cineol simultaneously with the stimuli in culture supernatants by enzyme immunoassay. Results: Therapeutic concentrations of 1,8-cineol (1.5 mug/ml = 10(-5) M) inhibited significantly (n = 13-19, p=0.0001) cytokine production in lymphocytes of TNF-alpha > IL-1beta > IL-4 > IL-5 by 92, 84, 70, and 65%, respectively. Cytokine production in monocytes of TNF-alpha > IL-1beta > IL-6 >IL-8 was also significantly (n = 7-16, p<0.001) inhibited by 99, 84, 76, and 65%, respectively. In the presence of 1,8-cineol (0.15 mug/ml = 10(-6) M) production of TNF-alpha >IL-1beta by monocytes and of IL-1beta > TNF-alpha by lymph-ocytes was significantly inhibited by 77, 61 and by 36, 16%, respectively. 1,8-cineol (10(-6) M) had a larger impact on TNF-alpha and IL-1beta-production in monocytes compared to lymphocytes (p<0.03) and similar effects (p>0.59) at therapeutically relevant concentrations of 1,8-Cineol (10(-5) M). Conclusion: These results characterize 1,8-cineol as strong inhibitor of TNF-alpha and IL-1beta and suggest smaller effects on chernotactic cytokines. This is increasing evidence for the role of 1,8-cineol to control airway mucus hypersecretion by cytokine inhibition, suggesting long-term treatment to reduce exacerbations in asthma, sinusitis and COPD. (C) 2004 Elsevier Ltd. All rights reserved.
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