LOCAL AIRWAYS IMMUNE MODIFICATIONS INDUCED BY ORAL BACTERIAL EXTRACTSIN CHRONIC-BRONCHITIS

Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal mod els and in normal humans, gut-associated lymphoid tissue (GALT) stimul ation is able to induce a generalized response by the whole mucosal-as sociated lymphoid tissue (MALT). The aim of this placebo-controlled, d ouble-blind, parallel-group study was to evaluate whether the stimulat ion of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either sys temically or locally in the respiratory tract in patients suffering fr om chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smoker s, and 9 ex-smokers) for at least 3 years. According to a balanced-blo ck randomization method, ten patients received active treatment and te n received placebo. Either drug or placebo was to be taken as one caps ule daily the first 10 days of 3 consecutive months. Each capsule of t he active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (TO) and 90 days after beginning of treat ment (T90), all patients underwent bronchoalveolar lavage (BAL) and pe ripheral blood withdrawal to assay BAL fluids and serum samples for im mune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatme nt (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.4 5, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading fron t stimulated motility and superoxide anion-O2--release) showed a signi ficant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13. 4, 8.1 to 28.8 mum, p=0.02) and of stimulated motility after FMLP 10(- 7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 mum, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1 .7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and aft er stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 2 2.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were n ot significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed. Our data demon strate that oral administration of a BE can increase immune defenses i n the respiratory tract of patients with chronic bronchitis, without a pparently altering systemic immunity. This confirms the possibility of a preferential traffic of immune information across the MALT and supp orts a rationale for experimental trials with oral treatments using BE s in the prevention of chronic bronchitis exacerbations.