Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with
inflammation. To restore this balance,
antioxidants are often suggested as
therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous
antioxidant quercetin, which has a versatile
antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of
quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced
endogenous antioxidant defense, shown by a reduced total
antioxidant capacity and lowered
glutathione and
uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with
quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory
cytokines IL-8 and TNFα. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of
bleomycin-triggered BEAS-2B cells, shows that
quercetin boosts the
antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory
cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of
quercetin to restore the disturbed redox balance and reduce
inflammation.