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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:1299-1306 (2008)
© 2008 The Gerontological Society of America

Diminished Acute Phase Response and Increased Hepatic Inflammation of Aged Rats in Response to Intraperitoneal Injection of Lipopolysaccharide

Christian R. Gomez, Claudio Acuña-Castillo, Claudio Pérez, Elías Leiva-Salcedo, Denise M. Riquelme, Gamaliel Ordenes, Kiyoko Oshima, Mauricio Aravena, Viviana I. Pérez, Sumiyo Nishimura, Valeria Sabaj, Robin Walter and Felipe Sierra

1 Instituto de Ciencias Biomédicas (ICBM), Centro FONDAP de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Santiago.
2 Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, USACH, Santiago.
3 Facultad de Ciencias de la Salud, Universidad Diego Portales, Santiago, Chile.
4 Escuela de Tecnología Médica, Facultad de Medicina, Universidad de Chile, Santiago.
5 Department of Pathology, Loyola University Medical Center, Maywood, Illinois.
6 The Lankenau Institute for Medical Research, Wynnewood, Philadelphia, Pennsylvania.

Address correspondence to Felipe Sierra, PhD, National Institute on Aging, NIA/NIH, 7201 Wisconsin Ave, Suite 2C231, Bethesda MD 20892. E-mail: sierraf{at}nia.nih.gov

Aging is associated with a deterioration of the acute phase response to inflammatory challenges. However, the nature of these defects remains poorly defined. We analyzed the hepatic inflammatory response after intraperitoneal administration of lipopolysaccharide (LPS) given to Fisher 344 rats aged 6, 15, and 22–23 months. Induction of the acute phase proteins (APPs), haptoglobin, {alpha}-1-acid glycoprotein, and T-kininogen was reduced and/or retarded with aging. Initial induction of interleukin-6 in aged rats was normal, but the later response was increased relative to younger counterparts. An exacerbated hepatic injury was observed in aged rats receiving LPS, as evidenced by the presence of multiple microabscesses in portal tracts, confluent necrosis, higher neutrophil accumulation, and elevated serum levels of alanine aminotransferase, relative to younger animals. Our results suggest that aged rats displayed a reduced expression of APPs and increased hepatic injury in response to the inflammatory insult.

Key Words: Liver • Inflammation • Injury • Acute phase response • Aging







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Copyright © 2008 by The Gerontological Society of America.