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Plasma esterases and inflammation in ageing and frailty

  • Pharmacokinetics and Disposition
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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References

  1. 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

    Article  PubMed  Google Scholar 

  2. 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

    PubMed  CAS  Google Scholar 

  3. 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

    PubMed  Google Scholar 

  4. Ershler WB (2007) A gripping reality: oxidative stress, inflammation, and the pathway to frailty. J Appl Physiol 103(1):3–5

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  6. 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

    Article  PubMed  CAS  Google Scholar 

  7. 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

    PubMed  Google Scholar 

  8. Morley JE, Baumgartner RN (2004) Cytokine-related aging process. J Gerontol A Biol Sci Med Sci 59(9):924–929

    Google Scholar 

  9. Hamerman D (1999) Toward an understanding of frailty. Ann Intern Med 130(11):945–950

    PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases and frailty. Annu Rev Med 51:245–270

    Article  PubMed  CAS  Google Scholar 

  13. 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

    PubMed  Google Scholar 

  14. 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

    PubMed  CAS  Google Scholar 

  15. Williams FM (1987) Serum enzymes of drug metabolism. Pharmacol Ther 34(1):99–109

    Article  PubMed  CAS  Google Scholar 

  16. Kampmann JP, Hansen JM (1981) Clinical pharmacokinetics of antithyroid drugs. Clin Pharmacokinet 6(6):401–428

    PubMed  CAS  Google Scholar 

  17. Kubo SH, Cody RJ (1985) Clinical pharmacokinetics of the angiotensin converting enzyme inhibitors. Clin Pharmacokinet 10(5):377–391

    Article  PubMed  CAS  Google Scholar 

  18. 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

    Article  PubMed  CAS  Google Scholar 

  19. Abou-Hatab K, O’Mahony MS, Patel S, Woodhouse K (2001) Relationship between age and plasma esterases. Age Ageing 30(1):41–45

    Article  PubMed  CAS  Google Scholar 

  20. 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

    Article  Google Scholar 

  21. 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

    Article  PubMed  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. 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

    Article  PubMed  CAS  Google Scholar 

  24. Publications of the Parliament of the United Kingdom. Available at: parliament.uk/pa/cm200405/cmselect/cmhealth/399/39902.htm

  25. 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

    CAS  Google Scholar 

  26. 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

    CAS  Google Scholar 

  27. 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

    CAS  Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. 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

    PubMed  CAS  Google Scholar 

  30. 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

    CAS  Google Scholar 

  31. 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

    Article  PubMed  Google Scholar 

  32. 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

    Article  PubMed  Google Scholar 

  33. 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

    PubMed  Google Scholar 

  34. 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

    PubMed  CAS  Google Scholar 

  35. Morgan ET (1997) Regulation of cytochrome p450 during inflammation and infection. Drug Metab Rev 29:1129–1188

    Article  PubMed  CAS  Google Scholar 

  36. Lally F, Crome P (2007) Understanding frailty. Postgrad Med J 83(975):16–20

    Article  PubMed  Google Scholar 

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Correspondence to Ruth E. Hubbard.

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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

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  • DOI: https://doi.org/10.1007/s00228-008-0499-1

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