A Yuengsrigul1, T W Chin, E Nussbaum. 1. Department of Pediatrics, Memorial Miller Children's Hospital, University of California, Irvine, USA.
Abstract
BACKGROUND: We have previously shown that children with mild asthma have a modest improvement in their pulmonary function tests after aerosolized furosemide. The mechanism of action is not known. The observation that furosemide possesses a similar profile of protection as sodium cromoglycate and nedocromil sodium suggests that furosemide may inhibit mediator production and release. OBJECTIVE: We studied the in vitro effects of furosemide on cytokine release from normal human peripheral blood mononuclear cells (PBMC) induced by E. coli lipopolysaccharide (LPS). METHODS: Peripheral blood mononuclear cells were isolated by density gradient centrifugation, stimulated with LPS and incubated at 37 degrees C with varying concentrations of furosemide, hydrocortisone, sodium cromoglycate, and nedocromil sodium for 24 hours. Supernatants were extracted and study for levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Intracellular IL-6 and TNF-alpha concentrations were also measured by cell cytometry. Cell viability was examined using XTT cell proliferation test and-measuring the release of lactate dehydrogenase (LDH). RESULTS: There was a significant reduction in levels of TNF-alpha and IL-6 at a furosemide concentration of 0.5 x 10(-2) M and a reduction in IL-8 levels at 10(-2) M. This inhibition was comparable to that found with equivalent molar concentrations of hydrocortisone. These findings were also confirmed with measurements of intracellular IL-6 and TNF-alpha by cell cytometry. High concentration of furosemide at 10(-2) M caused significant cellular cytotoxicity. CONCLUSION: These data suggest that furosemide may exhibit an anti-inflammatory effect. Specifically, the addition of furosemide resulted in decreased production of cytokines. This effect may be due to an immunosuppressive activity on monocytes as well as a direct cytotoxic effect at high furosemide concentrations.
BACKGROUND: We have previously shown that children with mild asthma have a modest improvement in their pulmonary function tests after aerosolized furosemide. The mechanism of action is not known. The observation that furosemide possesses a similar profile of protection as sodium cromoglycate and nedocromil sodium suggests that furosemide may inhibit mediator production and release. OBJECTIVE: We studied the in vitro effects of furosemide on cytokine release from normal human peripheral blood mononuclear cells (PBMC) induced by E. coli lipopolysaccharide (LPS). METHODS: Peripheral blood mononuclear cells were isolated by density gradient centrifugation, stimulated with LPS and incubated at 37 degrees C with varying concentrations of furosemide, hydrocortisone, sodium cromoglycate, and nedocromil sodium for 24 hours. Supernatants were extracted and study for levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8). Intracellular IL-6 and TNF-alpha concentrations were also measured by cell cytometry. Cell viability was examined using XTT cell proliferation test and-measuring the release of lactate dehydrogenase (LDH). RESULTS: There was a significant reduction in levels of TNF-alpha and IL-6 at a furosemide concentration of 0.5 x 10(-2) M and a reduction in IL-8 levels at 10(-2) M. This inhibition was comparable to that found with equivalent molar concentrations of hydrocortisone. These findings were also confirmed with measurements of intracellular IL-6 and TNF-alpha by cell cytometry. High concentration of furosemide at 10(-2) M caused significant cellular cytotoxicity. CONCLUSION: These data suggest that furosemide may exhibit an anti-inflammatory effect. Specifically, the addition of furosemide resulted in decreased production of cytokines. This effect may be due to an immunosuppressive activity on monocytes as well as a direct cytotoxic effect at high furosemide concentrations.
Authors: Sarika Chaudhari; Grace S Pham; Calvin D Brooks; Viet Q Dinh; Cassandra M Young-Stubbs; Caroline G Shimoura; Keisa W Mathis Journal: Front Physiol Date: 2022-06-13 Impact factor: 4.755