Central administration of the neurotensin receptor antagonist, SR48692, modulates diurnal and stress-related hypothalamic-pituitary-adrenal activity

BACKGROUND: The mechanism of bronchoobstruction in asthmatics following inhalation of lipopolysaccharide (LPS) is unclear. OBJECTIVE: In this study we have investigated the effects of the LPS on eosinophil survival rate in stimulating peripheral blood mononuclear cells (PBMCs) from patients with asthma. METHODS: PBMC supernatants from 10 asthmatic patients and 4 healthy subjects were compared for eosinophil survival rate using the same purified eosinophils. Two x 10(6) cells/ml of PBMCs were cultured for 24 hours in RPMI 1640 containing 10% fetal bovine serum along with 10 micrograms/ml of LPS. 10(6) cells/ml of eosinophils were incubated for 96 hours in the presence of PBMC-derived culture supernatants at 75% in volume. RESULTS: The viability of eosinophils incubated with PBMC supernatants from asthmatic patients stimulated with LPS was higher, 62.5% +/- 10.6% (mean +/- SD), than that without LPS, 26.9% +/- 10.8%, and also higher than that of PBMCs from healthy subjects with LPS, 40.0% +/- 15.4%. This increasing activity of asthmatic PBMC stimulated with LPS was markedly inhibited from 72.2% +/- 9.7% to 38.5% +/- 6.8% by addition of mouse anti-human GM-CSF antibody to the PBMC supernatant but not mouse anti-human IL-5 antibody. CONCLUSION: These results suggest that LPS enhances eosinophil survival in asthmatics by increasing the production of GM-CSF from PBMCs.