Advanced age exacerbates the pulmonary inflammatory response after lipopolysaccharide exposure.
OBJECTIVE
The aged population is at a higher risk of mortality as a result of complications of injury or infection, such as acute lung injury. The objective of this study was to analyze pulmonary inflammatory responses in young and aged mice after administration of lipopolysaccharide.


METHODS
Prospective, controlled laboratory study.


METHODS
Animal resource facilities and research laboratory.


METHODS
Young (2-3 months old) and aged (18-20 months old) female BALB/c mice.


METHODS
Animals received intraperitoneal injection of lipopolysaccharide derived from Pseudomonas aeruginosa. Control mice received saline alone. After 24 hrs, mice were killed. Pulmonary neutrophil infiltration was assessed histologically and by myeloperoxidase activity. Pulmonary levels of the CXC chemokines, monocyte inflammatory protein-2 and KC, and cytokines, tumor necrosis factor-alpha and interleukin-1beta, were assessed by enzyme-linked immunosorbent assay.


RESULTS
Lungs of aged mice given lipopolysaccharide showed a six-fold higher neutrophil infiltration and three-fold higher level of myeloperoxidase activity than lungs of young mice given lipopolysaccharide. Pulmonary levels of monocyte inflammatory protein-2 and KC were significantly higher in the lungs of aged mice given lipopolysaccharide, compared with younger mice. Levels of tumor necrosis factor-alpha and interleukin-1beta in the lung were analyzed as well. After lipopolysaccharide treatment, there was no difference in the level of tumor necrosis factor-alpha in lungs of young and aged animals, but interleukin-1beta was two-fold higher in the lungs of the aged group. These data suggest that at this time point, interleukin-1beta may contribute to the higher production of CXC chemokines observed in lungs of aged mice vs. young mice receiving lipopolysaccharide.


CONCLUSIONS
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.
Gomez
Christian R
CR
Department of Cell Biology, Neurobiology and Anatomy, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA.
Hirano
Stefanie
S
Cutro
Brent T
BT
Birjandi
Shirin
S
Baila
Horea
H
Nomellini
Vanessa
V
Kovacs
Elizabeth J
EJ
D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D019743:Chemokines, CXC / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology; D009195:Peroxidase / Q000032:analysis / Q000276:immunology; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
D019743:Chemokines, CXC; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase