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Interleukin-18 (IL-18) plays an important role in innate and acquired immunity, in particular against intracellular pathogens. However, little is known about the microbial factors that trigger IL-18 secretion by dendritic cells (DCs). To determine the influence of bacterial virulence factors on the activation and release of IL-18, we infected human monocyte-derived DCs with virulence mutants of the facultative intracellular pathogen Salmonella typhimurium. Our results show that infection by S. typhimurium causes caspase-1-dependent activation of IL-18 and triggers the release of IL-18 in human DCs. The secretion of IL-18 by the DCs was closely correlated with the ability of the S. typhimurium strains to induce apoptosis. We demonstrate that activation and release of IL-18 are blocked by mutations in the Salmonella sipB gene, which encodes a virulence factor that activates caspase-1 to induce apoptosis. These findings indicate that the activation and release of IL-18 induced by bacterial virulence factors may represent one component of innate immunity against the intracellular bacteria.

We conducted a randomized clinical trial to assess the effectiveness of a newly established education program for adults with asthma. The program was designed to improve patients' health and functional status. Hospitalized patients with asthma were randomly assigned to immediate education or a 6-month waiting list. The education program consisted of three group sessions, delivered by trained educators, and focused on improving patients' self-management skills. Of 253 eligible patients, 131 agreed to participate (66 assigned to immediate education, 65 controls) and 115 (88%) completed the follow-up assessment at 6 months. At follow-up, most indicators of self-management skills and health and functional status had improved significantly among educated patients, but similar improvements were also seen among controls. The trial arms differed significantly on only four variables: patients in the immediate-education group were more likely to develop confidence in their asthma treatment (odds ratio adjusted for baseline [OR] = 2.9; 95% confidence interval [CI]: 1.0 to 8.1), to improve their knowledge of correct inhalation technique (OR = 2.4; 95% CI: 1.0 to 5.7), and to improve knowledge of the peak flow reading that warrants calling a physician (OR = 3.1; 95% CI: 1.4 to 6.7), but they improved less on the Asthma Quality of Life Questionnaire "activity" score (difference: -0.4 on a 1 to 7 scale; 95% CI: -0.8 to 0.0). Use of health services during follow-up was similar in the two groups. The education program did not enhance patients' health and functional status, despite improving a few self-management skills. These results underscore the need for controlled evaluations of education programs.