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An animal model of the clearance of nontypable Haemophilus influenzae has been developed to determine both optimal immunization strategies for controlling colonization of the respiratory tract in patients with damaged airways and mechanisms of action of immune clearance. It was demonstrated that stimulation of gut-associated lymphoid tissue (GALT) (either by direct injection or by ingestion of antigen) followed by local administration of antigen into the bronchus was required to enhance clearance in this model. The primary effect of GALT immunization persisted for at least 6 wk; it was specific and could not be replaced by systemic immunization. Failure to stimulate locally in the bronchus was associated with protracted clearance. No clear correlation between local or systemic antibody and bacterial clearance was demonstrated; however, immunized rats were shown to have faster recruitment of phagocytic cells to the bronchial spaces, and these phagocytes had a higher activity state than cells harvested from nonimmunized animals. It is probable that bacterial clearance is accelerated in immunized animals due in part to factors mediating a change in the behavior of luminal phagocytes.

SUMMARY The role of mucosal fibroblasts in intestinal inflammatory reactions is not known. In this study, we demonstrate that fibroblasts grown from histologically normal human duodenal biopsy tissues expressed mRNA genes for granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). IL‐lα, IL‐1β, IL‐6, IL‐8, IL‐10, intercellular adhesion molecule‐I (ICAM‐I) and vascular cell adhesion molecule‐1 (VCAM‐i) when stimulated with lipopolysaccharide (LPS) or IL‐1α. The increased mRNA expression of GM‐CSF, IL‐1α IL‐1β IL‐6 and IL‐α in response to IL‐1α and LPS stimulation was time‐ and dose‐dependent. In contrast. IL‐10 was weakly expressed when fibroblasts were stimulated with LPS. IL‐1α or tumour necrosis factor‐alpha (TNF‐α), but the expression was enhanced in the presence of cycloheximide combined with optimal concentrations of LPS. IL‐1α or TNF‐α. IL‐1α was a more potent stimulator than LPS for GM‐CSF. IL‐6, IL‐8 and I L‐10 expression, but not for IL‐1α and IL‐1β. Increased GM‐CSF. lL‐6 and IL‐8 gene expression was associated with the production of cytokine proteins in culture supernatant, but IL‐1α and IL‐1bL remained undetectable. Dexamethasone suppressed both gene expression and protein production of GM‐CSF. IL‐6 and IL‐8 when fibroblasts were exposed to IL‐1α. TNF‐α stimulated the release of GM‐CSF. IL‐6 and IL‐8 and, combined with IL‐1α. cytokine production was enhanced synergistically. Finally, both LPS and IL‐1ã up‐regulated ICAM‐I and VCAM‐1 gene expression. These findings implicate duodenal fibroblasts in the initiation and/or regulation of intestinal inflammation.

Summary Pseudomonas aeruginosa., an oportunistic bacterial pathogen, is a major course of morbidity and mortality in subjects with compromised respiratory function despite the significant advances in therapeutic practices. The bacteria produces an armoury of products which modify its infective niche to ensure bacterial survival. The role of antibody in protection against pulmonary infection remains poorly defined. Protection appears to be associated with opsonizing antibody whilst some other antibody responses may be deleterious and promote further lung damage. Cell mediated responses are clearly important in protection against infection. This review proposes a vaccine strategy aimed at enhancing specific T cell responses in the lung which, through T cell-derived cytokines, drive the recruitment of neutrophils to the lung and the subsequent activation of these cells results in the clearance of bacteria from the lung.

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