Increased carrageenan-induced acute lung inflammation in old rats

Ageing is associated with increased susceptibility to lung infections and delayed resolution of pulmonary infiltrates. The purpose of this study was to investigate the effect of age on the onset of carrageenan-induced lung inflammation. When compared with carrageenan-treated young rats (3 months old), old rats (>18 months old) exhibited a preponderance of pleural exudation and polymorphonuclear cell infiltration. Lung myeloperoxidase activity, an index of neutrophil infiltration and activation, was significantly increased in old rats in comparison with young rats. Consistent with the biochemical markers of inflammation, increased lung damage, as assessed by nitrosative stress and lipid peroxidation, was observed in carrageenan-treated old rats. In the lung exudate obtained from old rats, a significant reduction in interleukin-10 (IL-10) was observed, while similar expression of monocyte chemotactic protein-1 was induced, suggesting that a decrease in IL-10 rather than increased chemotaxis may account for the preponderance of the inflammatory cellular infiltrate in old rats. Similar to the in vivo situation, freshly isolated alveolar macrophages obtained from old rats produced less IL-10. This defective IL-10 production could be explained by a reduction in the cAMP-dependent signalling pathway, which mediates IL-10 production. Indeed, we found decreased cAMP-responsive element binding protein (CREB) and phosphorous-CREB (P-CREB) expression in old rats, which may account for reduced IL-10 production in old rats.