Interferon-gamma (IFN-γ) treatment decreases the inflammatory response in chronic Pseudomonas aeruginosa pneumonia in rats

Abstract

SUMMARYIn a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied whether the inflammatory response could be altered by intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-). Rats were treated either before or after intratracheal challenge with P. aeruginosa embedded in alginate beads. Rats treated after challenge had a significant reduction in the severity of macroscopic lung inflammation compared with rats treated before challenge (P 0 : 004) and controls (P 0 : 003). The histopathology in controls was dominated by numerous polymorphonuclear leucocytes (PMN) ( 5 90%) surrounding the alginate beads like in CF. This could be caused by a Th2-like response. In contrast, a complete shift to a chronic-type inflammation dominated by mononuclear leucocytes ( 5 90% lymphocytes and plasma cells) and granulomas was observed in both rrIFN--treated groups of rats. This could be caused by a Th1-like response. There was no significant difference in lethality between the groups, and the antibody titres against P. aeruginosa sonicate and alginate were similar in the treated rats and controls. Since the ongoing lung tissue damage in CF patients has been shown to be caused by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our findings offer a possible new strategy of modifying the inflammatory response in CF patients.

Hpyerglycemic and anti-diabetic nephritis activities of polysaccharides separated from Auricularia auricular in diet-streptozotocin-induced diabetic rats

“…It is reported in one study that the association between cytokine-producing frequencies in αβ and γδT cells are as follows: TNF-α >IFN-γ >IL-2 (33). The beneficial role of the inflammatory cytokine IFN-γ has been confirmed by previous studies (34), and a lower IFN-γ secretion from T cells is found in patients with cystic fibrosis (35). Additionally, IFN-γ and TNF-α are reported to show suppressive effects on white blood cell precursors (36).…”

Pulmonary Inflammation Induced byPseudomonas aeruginosaLipopolysaccharide, Phospholipase C, and Exotoxin A: Role of Interferon Regulatory Factor 1

“…Therefore, in the absence of IRF-1, P. aeruginosa-induced inflammation develops in the context of reduced Th1 responses. Because Th1 cytokines seem to favor clearance of P. aeruginosa (16,29), the low levels of IRF-1 present in CF patients' epithelia (18) might contribute to the persistence of P. aeruginosa infection and the chronic inflammation of the CF patient lung. …”

Effects of bronchopulmonary inflammation induced by Pseudomonas aeruginosa on adenovirus-mediated gene transfer to airway epithelial cells in mice

“…[28][29][30][31][32][33][34] The histopathologic features of rats 35 and mice 36 inoculated with P. aeruginosaladen agarose beads closely mimics that of CF patients, which includes endobronchitis, bronchopneumonia, bronchiectasis, mucus plugging and alveolar exudates with acute and chronic inflammatory cells. The inoculation of sterile agarose beads is associated with minimal inflammation, 36 however, as confirmed in the current study.…”