Tetracyclines tigecycline and doxycycline inhibit LPS-induced nitric oxide production by RAW 264.7 murine macrophages. (101.3)

Abstract

We previously reported that minocycline and doxycycline strongly suppress serum IgE and decrease IgE production by PBMC from patients with asthma (Smith-Norowitz et al, Ann Allergy, Asthma, & Immunol 2002; 89:172–9; Durkin et al, AAAAI Annual Meeting San Diego, Feb 23–27, 2007). We have now studied the effects of doxycycline and tigecycline on LPS-induced nitric oxide (NO) production by murine macrophages (RAW 264.7). Cell cultures were incubated for 1 – 5 days with or without LPS (200ng/mL, phenol extracted from Salmonella typhimurium) and doxycycline or tigecycline (1 – 10 μg/ml). Accumulation of nitrite, stable metabolite of NO, was determined using a modified colorimetric Griess reaction. Both doxycycline, and to a lesser extent tigecycline, consistently suppressed LPS-induced nitric oxide production in dose-dependent manner (doxycycline: 23–30%, tigecycline: 10–23%). The tetracycline mediated suppression of NO production by macrophages in culture is independent of antimicrobial activities, but the underlying mechanism of this effect remains to be elucidated. Since nitric oxide is an important mediator of inflammatory responses, our results suggest that the anti-inflammatory effects of tetracyclines may be utilized in the treatment of IgE mediated allergic disorders and may decrease exhaled breath nitric oxide, an emerging biomarker of allergic airway disease.