Abstract
Objectives
Esterases are enzymes of drug metabolism known to be reduced in frail older people and during acute illness. The mechanism for this is unknown. The aim of this study was to examine esterase activity and inflammation in ageing and frailty.
Methods
Thirty frail patients (mean age 84.9 years) dependent on continuing inpatient care, 40 patients of intermediate frailty attending Day Hospital (84.2 years), 40 fit older controls (82.7 years) and 30 young controls (23.3 years) were studied. Frailty indicators, plasma esterase activities and markers of inflammation were measured.
Results
With increasing patient frailty, C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) increased significantly and esterase activity, with the exception of aspirin esterase, fell significantly (p < 0.005). There were significant negative correlations between log-transformed IL-6 and acetylcholinesterase (r = −0.354, p < 0.01), butyrylcholinesterase (r = −0.392, p < 0.01) and benzoylcholinesterase activity (r = −0.241, p < 0.05) and significant negative correlations between TNF-α and acetylcholinesterase (r = −0.223, p < 0.01), butyrylcholinesterase (r = −0.279, p < 0.01) and benzoylcholinesterase activity (r = −0.253, p < 0.01). Aspirin esterase activity did not correlate with IL-6 or TNF- α.
Conclusion
Frailty was associated with higher inflammatory markers and lower esterase activity. There was a weak but significant negative correlation between both IL-6 and TNF-α and the activity of three of four esterases. The negative correlation between esterase activity and inflammatory markers may have a causal basis, comparable to the inflammatory suppression of cytochrome P-450 enzymes.
Similar content being viewed by others
References
Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, Ershler WB, Harris T, Fried LP (2006) Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 54(6):991–1001
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56(3):M146–M156
Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, Zeger SL, Fried LP (2006) Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci 61(3):262–266
Ershler WB (2007) A gripping reality: oxidative stress, inflammation, and the pathway to frailty. J Appl Physiol 103(1):3–5
Maggio M, Cappola AR, Ceda GP, Basaria S, Chia CW, Valenti G, Ferrucci L (2005) The hormonal pathway to frailty in older men. J Endocrinol Invest 28[11 Suppl Proc]:15–19
Howard C, Ferrucci L, Sun K, Fried LP, Walston J, Varadhan R, Guralnik JM, Semba RD (2007) Oxidative protein damage is associated with poor grip strength among older women living in the community. J Appl Physiol 103(1):17–20
Michelon E, Blaum C, Semba RD, Xue QL, Ricks MO, Fried LP (2006) Vitamin and carotenoid status in older women: associations with the frailty syndrome. J Gerontol A Biol Sci Med Sci 61(6):600–607
Morley JE, Baumgartner RN (2004) Cytokine-related aging process. J Gerontol A Biol Sci Med Sci 59(9):924–929
Hamerman D (1999) Toward an understanding of frailty. Ann Intern Med 130(11):945–950
Roubenoff R, Parise H, Payette HA, Abad LW, D’Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB (2003) Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 115(6):429–435
Bruunsgaard H, Andersen-Ranberg K, Hjelmborg JB, Pedersen BK, Jeune B (2003) Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med 115(4):278–283
Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases and frailty. Annu Rev Med 51:245–270
Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59(3):242–248
Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47(6):639–646
Williams FM (1987) Serum enzymes of drug metabolism. Pharmacol Ther 34(1):99–109
Kampmann JP, Hansen JM (1981) Clinical pharmacokinetics of antithyroid drugs. Clin Pharmacokinet 6(6):401–428
Kubo SH, Cody RJ (1985) Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors. Clin Pharmacokinet 10(5):377–391
Yelland C, Summerbell J, Nicholson E, Herd B, Wynne H, Woodhouse KW (1991) The association of age with aspirin esterase activity in human liver. Age Ageing 20(1):16–18
Abou-Hatab K, O’Mahony MS, Patel S, Woodhouse K (2001) Relationship between age and plasma esterases. Age Ageing 30(1):41–45
O’Mahony MS, George G, Westlake H, Woodhouse K (1994) Plasma aspirin esterase activity in elderly patients undergoing elective hip replacement and with fractured neck of femur. Age Ageing 23(4):338–341
White S, Calver BL, Newsway V, Wade R, Patel S, Bayer A, O’Mahony MS (2005) Enzymes of drug metabolism during delirium. Age Ageing 34(6):603–608
Abou-Hatab K, Ganeshalingam K, O’Mahony MS, Giurani F, Patel S, Woodhouse K (2001) The effect of community-acquired pneumonia on plasma esterases in older people. Eur J Clin Pharmacol 57(1):55–60
Williams FM, Wynne H, Woodhouse KW, Rawlins MD (1989) Plasma aspirin esterase: the influence of old age and frailty. Age Ageing 18(1):39–42
Publications of the Parliament of the United Kingdom. Available at: parliament.uk/pa/cm200405/cmselect/cmhealth/399/39902.htm
Simonsick EM, Gardner AW, Poehlman ET (2000) Assessment of physical function and exercise tolerance in older adults: reproducibility and comparability of 5 measures. Aging Clin Exp Res 12:274–280
Brazier JE, Harper R, Jones NM, O’Cathain A, Thomas KJ, Usherwood T, Westlake L (1992) Validating the SF-36 health survey questionnaire: new outcome measure for primary care. Br Med J 305:160–164
Pedersen AN, Ovesen L, Shroll M, Avlund K, Era P (2002) Body composition of 80-years old men and women and its relation to muscle strength, physical ability and functional ability. J Nutr Health Ageing 6:413–420
Ellman GL, Courtney KD, Andres V Jr, Feather-stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Williams FM, Mutch EM, Nicholson E, Wynne H, Wright P, Lambert D, Rawlins MD (1989) Human liver and plasma aspirin esterase. J Pharm Pharmacol 41(6):407–409
Kalow W, Lindsay HA (1955) A comparison of optical and manometric methods for the assay of human serum cholinesterase. Can J Med Sci 33(4):568–574
Leng SX, Xue Q-L, Tian J, Walston JD, Fried LP (2007) Inflammation and frailty in older women. J Am Geriatr Soc 55:864–871
Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, Gottdiener J, Fried LP (2002) Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med 162(20):2333–2341
Bergman H, Ferrucci L, Guralnik J, Hogan DB, Hummel S, Karunananthan S, Wolfson C (2007) Frailty: an emerging research and clinical paradigm–issues and controversies. J Gerontol A Biol Sci Med Sci 62(7):731–737
Hogan DB, Ebly EM, Fung TS (1999) Disease, disability, and age in cognitively intact seniors: results from the Canadian Study of Health and Aging. J Gerontol A Biol Sci Med Sci 54(2):M77–M82
Morgan ET (1997) Regulation of cytochrome p450 during inflammation and infection. Drug Metab Rev 29:1129–1188
Lally F, Crome P (2007) Understanding frailty. Postgrad Med J 83(975):16–20
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hubbard, R.E., O’Mahony, M.S., Calver, B.L. et al. Plasma esterases and inflammation in ageing and frailty. Eur J Clin Pharmacol 64, 895–900 (2008). https://doi.org/10.1007/s00228-008-0499-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-008-0499-1