title: Imparied interferon-gamma production by peripheral blood mononuclear cells and effects of calcitriol in pulmonary sarcoidosis.
abstract: Pulmonary sarcoidosis (S) is a granulomatous disease of unknown etiology characterized by spontaneous release of cytokines and 1,25-dihydroxyvitamin D3 (calcitriol) at the sites of granulomatous reaction. Stimulated by our previous findings that high levels of interferon-gamma (IFN-gamma) occur in this disease and that calcitriol reduces IFN-gamma production by peripheral blood mononuclear cells (PBMC) from normal subjects, we designed the present study to evaluate IFN-gamma production and the effect of calcitriol on the release of this cytokine by PBMC in S patients. The cells were stimulated with staphylococcal enterotoxin A (SEA) and A23187 calcium ionophore. Our results show that SEA- and A23187-stimulated PBMC from patients with S released significantly less IFN-gamma than those from control subjects. Calcitriol at 10(-6) M and 10(-9) M concentrations reduced IFN-gamma production by SEA-stimulated PBMC but this inhibitory effect was lower in S patients than controls. With A23187 we observed different behaviour at the various doses: at low doses calcitriol was as effective as in controls, but at 10(-6) M it was significantly less inhibitory in S than in healthy subjects.
authors.affiliation: Institute of General Physiology, University of Siena, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Rottoli
authors.forename: M
authors.initials: M
authors.lastname: Muscettola
authors.forename: G
authors.initials: G
authors.lastname: Grasso
authors.forename: M G
authors.initials: MG
authors.lastname: Perari
authors.forename: M
authors.initials: M
authors.lastname: Vagliasindi
mesh_terms: D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*
chemical_list: D004768:Enterotoxins; D007369:Interferon Inducers; C026066:enterotoxin A, Staphylococcal; D000001:Calcimycin; D007371:Interferon-gamma; D002117:Calcitriol