The effects of cortisone treatment and burn injury on plasma and lung lavage cortisol concentrations and alveolar macrophage activity.
Thermal injury often results in the development of compromised host defense mechanisms against infections (eg, increased incidence of pulmonary sepsis in postburn animals has been attributed to impaired cellular defenses in the lung). Recent reports have demonstrated that high dose glucocorticoid therapy used in the treatment of inflammatory diseases and shock also results in an increased susceptibility of the host to pulmonary sepsis. Although several defense mechanisms are available to the respiratory tract combating bacterial challenges, the major cellular defense is the alveolar macrophage, which phagocytizes infectious agents and potentially toxic particulate matter that infiltrate the lower respiratory tract. Recent evidence has demonstrated that high doses of cortisol in vivo impair both functional and metabolic activities of the alveolar macrophage. However, there is little information regarding whether alterations in endogenous levels of glucocorticoids following systemic injury can mediate similar defects on the cellular defenses of the lung. The present study demonstrated that both high dose glucocorticoid treatment and burn injury severely impaired the functional activity of the resident lung macrophage. The phagocytic cell population in the lower respiratory tract was reduced by more than 50%, 24 hr following either burn injury or a 7 day cortisone regimen. Furthermore, the remaining alveolar macrophages lavaged from either experimental group demonstrated a marked impairment in phagocytic activity. The combination of a reduced macrophage population in the lung and a decreased phagocytic activity of the residual cells indicated a severe deficiency in the total lung phagocytic capacity. The 7 day cortisone treatment markedly elevated plasma (greater than 400%) and lung lavage (greater than 200%) levels of cortisol. Although plasma levels of cortisol were also significantly increased (greater than 50%) 24 hr post burn injury, lung lavage cortisol levels were not higher than saline-treated sham burn control values. However, lung lavage concentration of cortisol was increased over threefold following cortisone treatment and burn injury.
D000818:Animals; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D003348:Cortisone / Q000494:pharmacology*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000032:analysis* / Q000097:blood; D008168:Lung / Q000032:analysis*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D007507:Therapeutic Irrigation
D003348:Cortisone; D006854:Hydrocortisone