title: Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro.
abstract: Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection.
authors.affiliation: Hôpital l'Aiguelongue, Montpellier, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Pujol
authors.forename: B
authors.initials: B
authors.lastname: Klein
authors.forename: P
authors.initials: P
authors.lastname: Godard
authors.forename: L
authors.initials: L
authors.lastname: Dussourd d'Hinterland
authors.forename: F B
authors.initials: FB
authors.lastname: Michel
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000494:pharmacology*; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000276:immunology; D011897:Random Allocation
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D007375:Interleukin-1; D008070:Lipopolysaccharides; C034206:Ribomunyl