Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure

Gómez, Christian R.; Hirano, Stefanie A.; Cutro, Brent T.; Birjandi, Shirin; Baila, Horea; Nomellini, Vanessa; Kovacs, Elizabeth J.

doi:10.1097/01.ccm.0000251639.05135.e0

Cited by 97 publications

(62 citation statements)

References 52 publications

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“…Accordingly, we also found approximately twice the number of neutrophils in the lungs of aged mice following challenge at this time point. A similar finding was reported by Gomez et al who, after intraperitoneal injection of lipopolysaccharide (LPS) in mice, observed significantly increased alveolar cell counts in aged mice compared to young counterparts 36 . While poor chemotaxis of neutrophils from old donors has been reported 37 , those studies were performed using human neutrophils isolated from whole blood.…”

Section: Discussionsupporting

confidence: 87%

Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury

Linge

Lee

Ochani

et al. 2015

Experimental Lung Research

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Background Acute lung injury (ALI) is a significant source of morbidity and mortality in critically ill patients. Age is a major determinant of clinical outcome in ALI. The increased ALI-associated mortality in the older population suggests that there are age-dependent alterations in the responses to pulmonary challenge. The objective of this observational study was to evaluate age-dependent differences in the acute (within 6hrs) immunological and physiological responses of the heart and lung, to pulmonary challenge, that could result in increased severity. Methods Male C57Bl/6 mice (young: 2–3 months, old: 18–20 months) were challenged intratracheally with cell wall components from gram positive bacteria (lipoteichoic acid and peptidoglycan). After 6h, both biochemical and physiological consequences of the challenge were assessed. Alveolar infiltration of inflammatory cells and protein, airspace and blood cytokines, cardiac function and myocardial proteasome activity were determined. Results In young mice there was a dose dependent response to pulmonary challenge resulting in increased airspace neutrophil counts, lung permeability, and concentrations of cytokines in bronchoalveolar lavage fluid and plasma. A midrange dose was then selected to compare the responses in young and old animals. In comparison, the old animals displayed increased neutrophil accumulation in the airspaces, decreased arterial oxygen saturation, body temperatures, plasma cytokine concentrations, and a lack of myocardial proteasome response, following challenge. Conclusions Age dependent differences in the onset of systemic response and in maintenance of vital functions, including temperature control, oxygen saturation and myocardial proteasome activation, are evident. We believe a better understanding of these age-related consequences of ALI can lead to more appropriate treatments in the elderly patient population.

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Section: Discussionsupporting

confidence: 87%

Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury

Linge

Lee

Ochani

et al. 2015

Experimental Lung Research

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“…Gomez et al . [21] inoculated lipopolysaccharide (from P. aeruginosa ) into the lungs of BALB/c mice and observed that the transcription levels of MIP-2 and KC in elderly mice were markedly higher than in young mice. In addition, PMN infiltration was greater in the elderly group.…”

Section: Discussionmentioning

confidence: 99%

Aging Reduces the Expression of Lung CINC and MCP-1 mRNA in a P. aeruginosa Rat Model of Infection

Wen

et al. 2014

Inflammation

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We investigated dynamic changes of inflammatory cell infiltration and expression of cytokine-induced neutrophil chemoattractant (CINC) and monocyte chemoattractant protein-1 (MCP-1) mRNA in aged rats with Pseudomonas aeruginosa pulmonary infection. Disease manifestation and lung tissue pathology (lesion dispersion, inflammatory reactions, tissue edema and bleeding) were more severe in aged rats than young rats. At various time points, lung tissue polymorphonuclear neutrophil and mononuclear macrophage numbers were lower in the aged group than the young group (P < 0.05), and at 24 h there was no difference in mononuclear macrophage numbers. After inoculation with P. aeruginosa, CINC and MCP-1 mRNA expression increased in both groups, but the peak lagged in old rats compared with young. Thus, aging can reduce the expression of CINC and MCP-1 mRNA in lung tissues, and reduce the infiltration of neutrophils and monocyte–macrophages induced by CINC and MCP-1. This might lead to increased risk of pneumonia in elderly patients.

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“…In humans and animals, acute lung injury is generally more serious and is associated with higher mortality at advanced ages (Antonini et al 2001;Ely et al 2002;Gomez et al 2007). We have previously reported prolonged and enhanced neutrophilic inflammation in the lungs of aged mice, as compared with young mice, after LPS intratracheal administration, in which age-related decreases in lung VEGF expression and prolonged overexpression of neutrophilic chemokines were observed (Ito et al 2005(Ito et al , 2007.…”

Section: Introductionmentioning

confidence: 93%

Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages

et al. 2008

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Lung injuries are generally more serious and cause high mortality in aged humans and animals. Heme oxygenase-1 (HO-1) is known to be readily inducible in alveolar macrophages (AMs) and airway epithelial cells to confer cytoprotection against oxidative stress. We thus investigated whether aging impairs the stress-induced upregulation of HO-1. In this study, we first quantified basal levels of HO-1 expression in lungs from male ICR mice of various ages. Second, young (9-11 weeks) and old (65-66 weeks) mice were subjected to intratracheal administration of lipopolysaccharide (LPS) and expression of HO-1 in the lungs was quantified at 2, 24 and 72 h. HO-1 expression in bronchiolar epithelial cells harvested by laser capture microdissection (LCM) was also specifically quantified in the two age groups. Third, we examined HO-1 expression in AMs lavaged from 22-week-old and 86-96-week-old male ICR mice in response to LPS for 24 h in vitro. We found that basal expression of HO-1 in the lungs did not differ with age. LPS-induced HO-1 upregulation was significantly impaired in the lungs of 65-66-week-old mice than in 9-11-week-old mice at 2 and 24 h, although there were no differences in the magnitude of HO-1 upregulation in bronchiolar epithelium at 2 h. LPS-induced upregulation of HO-1 was observed in AMs from 22-week-old mice (1.8-fold), but not in AMs from 86-96-week-old mice in vitro. In summary, we demonstrated age-related defects in HO-1 induction in the whole lungs and in AMs in response to LPS.

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Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure

Abstract: The hyperreactive systemic inflammatory response seen in aged individuals after lipopolysaccharide administration is accompanied by an exacerbated pulmonary inflammatory response, which may contribute to the higher mortality seen in the aged given an inflammatory insult.

Cited by 97 publications

References 52 publications

Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury

Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury

Aging Reduces the Expression of Lung CINC and MCP-1 mRNA in a P. aeruginosa Rat Model of Infection

Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages

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