title: Age-dependent alterations in the inflammatory response to pulmonary challenge.
abstract: The aging lung is increasingly susceptible to infectious disease. Changes in pulmonary physiology and function are common in older populations, and in those older than 60 years, pneumonia is the major cause of infectious death. Understanding age-related changes in the innate and adaptive immune systems, and how they affect both pulmonary and systemic responses to pulmonary challenge are critical to the development of novel therapeutic strategies for the treatment of the elderly patient. In this observational study, we examined age-associated differences in inflammatory responses to pulmonary challenge with cell wall components from Gram-positive bacteria. Thus, male Sprague-Dawley rats, aged 6 months or greater than 18 months (approximating humans of 20 and 55-65 years), were challenged, intratracheally, with lipoteichoic acid and peptidoglycan. Cellular and cytokine evaluations were performed on both bronchoalveolar lavage fluid (BAL) and plasma, 24 h post-challenge. The plasma concentration of free thyroxine, a marker of severity in non-thyroidal illness, was also evaluated. The older animals had an increased chemotactic gradient in favor of the airspaces, which was associated with a greater accumulation of neutrophils and protein. Furthermore, macrophage migration inhibitory factor (MIF), an inflammatory mediator and putative biomarker in acute lung injury, was increased in both the plasma and BAL of the older, but not young animals. Conversely, plasma free thyroxine, a natural inhibitor of MIF, was decreased in the older animals. These findings identify age-associated inflammatory/metabolic changes following pulmonary challenge that it may be possible to manipulate to improve outcome in the older, critically ill patient.
authors: Center for Heart and Lung Research, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
authors: Helena M
authors: HM
authors: Linge
authors: Center for Heart and Lung Research, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
authors: Kanta
authors: K
authors: Ochani
authors: Center for Heart and Lung Research, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
authors: Ke
authors: K
authors: Lin
authors: Center for Heart and Lung Research, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.
authors: Ji Young
authors: JY
authors: Lee
authors: Center for Heart and Lung Research, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA. emiller@nshs.edu.|Departments of Molecular Medicine, Medicine and Surgery, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, 11549, USA. emiller@nshs.edu.
authors: Edmund J
authors: EJ
authors: Miller
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002633:Chemotaxis; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D010457:Peptidoglycan / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013682:Teichoic Acids / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D010457:Peptidoglycan; D013682:Teichoic Acids; C009900:lipoteichoic acid; D013974:Thyroxine
keywords: Acute lung injury; Aging; Pneumonia; Thyroxine