Grain dust induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A.
Jagielo-PJ; Quinn-TJ; Qureshi-N; Schwartz-DA
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa and the Department of Bacteriology, University of Wisconsin, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin 1996 Jan; :1-26
The efficacy of pentaacylated diphosphoryl-lipid-A derived from the lipopolysaccharide (LPS) of Rhodobacter-spheroides (RsDPLA) was examined as a competitive inhibitor of grain dust induced airway inflammation. TTHP-1 cells were incubated with RsDPLA, LPS, or cotton dust extract (CDE). Incubation with RsDPLA revealed TNF-alpha stimulatory effects at 1, 10 and 100 micrograms/milliliter. Incubation with LPS or CDE resulted in TNF-alpha release at 0.02 microgram/milliliter. Pretreatment of THP-1 cells with varying concentrations of RsDPLA prior to incubation with LPS or CDE resulted in a dose dependent reduction in the LPS or CDE induced tumor necrosis factor alpha (TNF-alpha) release. The unique LPS inhibitory property of RsDPLA was used to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. No significant inflammatory response was caused by 10 micrograms of RsDPLA intratracheally in comparison to intratracheal saline. Pretreatment with RsDPLA intratracheally prior to exposure to CDE or LPS resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, TNF-alpha, and interleukin-6 compared to mice pretreated with sterile saline. The authors conclude that LPS inhibitory effect of RsDPLA is confirmed.
NIOSH-Grant; Pulmonary-system-disorders; Lung-irritants; Organic-dusts; Dust-exposure; Inhalants; Inhalation-studies; Grain-dusts; In-vitro-studies; In-vivo-studies; Laboratory-animals
Internal Medicine University of Iowa 200 Hawkins Drive Iowa City, IA 52242-1081
Final Grant Report
NTIS Accession No.
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa and the Department of Bacteriology, University of Wisconsin, William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin
University of Iowa, Iowa City, Iowa