European Journal of Applied Physiology

, Volume 114, Issue 8, pp 1737–1748 | Cite as

Resistance exercise training-induced decrease in circulating inflammatory CD14+CD16+ monocyte percentage without weight loss in older adults

  • Melissa M. Markofski
  • Michael G. Flynn
  • Andres E. Carrillo
  • Cheryl L. H. Armstrong
  • Wayne W. Campbell
  • Darlene A. Sedlock
Original Article



Exercise training reduces systemic inflammation in weight-stable people, but concurrent diet-induced body weight loss is not well studied. We hypothesized that resistance training would decrease inflammatory monocyte percentage and improve biomarkers associated with disease risk, independent of weight loss.


Forty physically inactive (PI) subjects (58.0 ± 5.7 years; BMI 30.1 ± 4.3 kg m−2) completed baseline testing, and 26 of these subjects completed 12-week of resistance training exercises while consuming either their usual, weight-maintenance diet (RE, n = 14) or an energy-restricted diet (RE–ER, n = 12). Nine physically active (PA) subjects served as a comparison group (60.1 ± 6.1 years; BMI 25.8 ± 3.1 kg m−2).


At baseline, circulating CD14+CD16+ monocyte percentage, C-reactive protein, and cholesterol were higher in PI vs. PA. Post-intervention, RE subjects had a ~35 % decrease in circulating CD14+CD16+, and a lower LPS-stimulated TNFα and IL-6 production, while RE–ER subjects had lower cholesterol than RE.


These findings indicate that resistance training is an effective means for older, overweight adults to reduce systemic inflammation. The unexpected lack of response with concurrent energy restriction underscores the need for further research on the use of resistance training and diet to reduce inflammation.


Resistance exercise Inflammation Adiponectin Cytokine 



Body mass index


C-reactive protein


Resistance exercise group


Resistance exercise and energy restriction group






Mean fluorescence intensity


Physically active


Physically inactive


Polymixin B


Toll-like receptor


Tumor necrosis factor



This research was conducted at Purdue University, West Lafayette, Indiana. Support for this project was provided by the National Institutes of Health, Indiana Clinical and Translational Sciences Institute, Indiana Clinical Research Center at Purdue University, UL RR025761; The Purdue University Ismail Center for Health, Exercise, and Nutrition; the Department of Health and Kinesiology at Purdue University; and a Bilsland Dissertation Fellowship (for MMM) from Purdue University.


  1. Adamopoulos S, Parissis J, Kroupis C, Georgiadis M, Karatzas D, Karavolias G, Koniavitou K, Coats AJ, Kremastinos DT (2001) Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. Eur Heart J 22(9):791–797PubMedCrossRefGoogle Scholar
  2. Adamopoulos S, Parissis J, Karatzas D, Kroupis C, Georgiadis M, Karavolias G, Paraskevaidis J, Koniavitou K, Coats AJ, Kremastinos DT (2002) Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure. J Am Coll Cardiol 39(4):653–663PubMedCrossRefGoogle Scholar
  3. Ahmed HM, Blaha MJ, Nasir K, Rivera JJ, Blumenthal RS (2012) Effects of physical activity on cardiovascular disease. Am J Cardiol 109(2):288–295. doi: 10.1016/j.amjcard.2011.08.042 PubMedCrossRefGoogle Scholar
  4. Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, Fallucca S, Alessi E, Letizia C, Jimenez A, Fallucca F, Pugliese G (2009) Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiovasc Dis. doi: 10.1016/j.numecd.2009.04.015 PubMedGoogle Scholar
  5. Barzilay J, Freedland E (2003) Inflammation and its association with glucose disorders and cardiovascular disease. Treat Endocrinol 2(2):85–94PubMedCrossRefGoogle Scholar
  6. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17(1):4–12PubMedGoogle Scholar
  7. Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L (2002) The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 168(7):3536–3542PubMedCrossRefGoogle Scholar
  8. Boule NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C (2005) Effects of exercise training on glucose homeostasis: the HERITAGE family study. Diabetes Care 28(1):108–114 (pii:28/1/108)PubMedCrossRefGoogle Scholar
  9. Castaneda C, Gordon PL, Parker RC, Uhlin KL, Roubenoff R, Levey AS (2004) Resistance training to reduce the malnutrition-inflammation complex syndrome of chronic kidney disease. Am J Kidney Dis 43(4):607–616PubMedCrossRefGoogle Scholar
  10. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334(5):292–295PubMedCrossRefGoogle Scholar
  11. Cottam D, Schaefer P, Shaftan G, Velcu L, Angus L (2002) Effect of surgically-induced weight loss on leukocyte indicators of chronic inflammation in morbid obesity. Obes Surg 12(3):335–342PubMedCrossRefGoogle Scholar
  12. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G (1997) Insulin resistance and hypersecretion in obesity. European Group for the study of insulin resistance (EGIR). J Clin Invest 100(5):1166–1173. doi: 10.1172/JCI119628 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Flynn MG, McFarlin BK, Phillips MD, Stewart LK, Timmerman KL (2003) Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women. J Appl Physiol 95(5):1833–1842PubMedGoogle Scholar
  14. Geffken DF, Cushman M, Burke GL, Polak JF, Sakkinen PA, Tracy RP (2001) Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 153(3):242–250PubMedCrossRefGoogle Scholar
  15. Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15(2):475–482PubMedCrossRefGoogle Scholar
  16. Hambrecht R, Fiehn E, Weigl C, Gielen S, Hamann C, Kaiser R, Yu J, Adams V, Niebauer J, Schuler G (1998) Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98(24):2709–2715PubMedCrossRefGoogle Scholar
  17. Hanai H, Iida T, Takeuchi K, Watanabe F, Yamada M, Kikuyama M, Maruyama Y, Iwaoka Y, Hirayama K, Nagata S, Takai K (2008) Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease. Am J Gastroenterol 103(5):1210–1216. doi: 10.1111/j.1572-0241.2007.01714.x PubMedCrossRefGoogle Scholar
  18. Harris JA, Benedict FG (1919) A biometric study of basal metabolism in man. Carnegie Institution of Washington publication no. 279. Carnegie Institution of Washington, WashingtonGoogle Scholar
  19. Hu FB, Sigal RJ, Rich-Edwards JW, Colditz GA, Solomon CG, Willett WC, Speizer FE, Manson JE (1999) Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study. JAMA 282(15):1433–1439 (pii:joc90446)PubMedCrossRefGoogle Scholar
  20. Isasi CR, Deckelbaum RJ, Tracy RP, Starc TJ, Berglund L, Shea S (2003) Physical fitness and C-reactive protein level in children and young adults: the Columbia University BioMarkers study. Pediatrics 111(2):332–338PubMedCrossRefGoogle Scholar
  21. Janeway C (2005) Immunobiology: the immune system in health and disease, 6th edn. Garland Science, New YorkGoogle Scholar
  22. Katzel LI, Bleecker ER, Colman EG, Rogus EM, Sorkin JD, Goldberg AP (1995) Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle-aged and older men. A randomized controlled trial. JAMA 274(24):1915–1921PubMedCrossRefGoogle Scholar
  23. Keylock K, Lowder T, Leifheit K, Cook M, Mariani R, Ross K, Kim K, Chapman-Novakofski K, McAuley E, Woods J (2007) Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly. J Appl Physiol 102(3):1090–1098PubMedCrossRefGoogle Scholar
  24. Kohut ML, McCann DA, Russell DW, Konopka DN, Cunnick JE, Franke WD, Castillo MC, Reighard AE, Vanderah E (2006) Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun 20(3):201–209. doi: 10.1016/j.bbi.2005.12.002 PubMedCrossRefGoogle Scholar
  25. Marfella R, Esposito K, Siniscalchi M, Cacciapuoti F, Giugliano F, Labriola D, Ciotola M, Di Palo C, Misso L, Giugliano D (2004) Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care 27(1):47–52PubMedCrossRefGoogle Scholar
  26. McFarlin BK, Flynn MG, Campbell WW, Stewart LK, Timmerman KL (2004) TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Med Sci Sports Exerc 36(11):1876–1883PubMedCrossRefGoogle Scholar
  27. McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Stewart LK, Timmerman KL, Coen PM (2006) Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. J Gerontol A Biol Sci Med Sci 61(4):388–393PubMedCrossRefGoogle Scholar
  28. Newsom SA, Schenk S, Thomas KM, Harber MP, Knuth ND, Goldenberg N, Horowitz JF (2009) Energy deficit after exercise augments lipid mobilization but does not contribute to the exercise-induced increase in insulin sensitivity. J Appl Physiol. doi: 10.1152/japplphysiol.01106.2009 PubMedCentralPubMedGoogle Scholar
  29. Pedersen BK, Fischer CP (2007a) Beneficial health effects of exercise–the role of IL-6 as a myokine. Trends Pharmacol Sci 28(4):152–156. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  30. Pedersen BK, Fischer CP (2007b) Physiological roles of muscle-derived interleukin-6 in response to exercise. Curr Opin Clin Nutr Metab Care 10(3):265–271. doi: 10.1097/MCO.0b013e3280ebb5b3 PubMedCrossRefGoogle Scholar
  31. Plomgaard P, Nielsen AR, Fischer CP, Mortensen OH, Broholm C, Penkowa M, Krogh-Madsen R, Erikstrup C, Lindegaard B, Petersen AM, Taudorf S, Pedersen BK (2007) Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia 50(12):2562–2571. doi: 10.1007/s00125-007-0834-6 PubMedCrossRefGoogle Scholar
  32. Roberts CK, Won D, Pruthi S, Lin SS, Barnard RJ (2006) Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men. Diabetes Res Clin Pract 73(3):249–259. doi: 10.1016/j.diabres.2006.02.013 PubMedCrossRefGoogle Scholar
  33. Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M, Cremers B, Grenner Y, Geisel J, Schlitt A, Kohler H, Fliser D, Girndt M, Heine GH (2009) Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J. doi: 10.1093/eurheartj/ehp308 PubMedGoogle Scholar
  34. Schlitt A, Heine GH, Blankenberg S, Espinola-Klein C, Dopheide JF, Bickel C, Lackner KJ, Iz M, Meyer J, Darius H, Rupprecht HJ (2004) CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb Haemost 92(2):419–424. doi: 10.1267/THRO04080419 PubMedGoogle Scholar
  35. Siri WE (1956) The gross composition of the body. Adv Biol Med Phys 4:239–280PubMedCrossRefGoogle Scholar
  36. Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285(2):E433–E437PubMedGoogle Scholar
  37. Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, Ritter PL (2001) CHAMPS physical activity questionnaire for older adults: outcomes for interventions. Med Sci Sports Exerc 33(7):1126–1141PubMedCrossRefGoogle Scholar
  38. Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, McFarlin BK, Timmerman KL, Coen PM, Felker J, Talbert E (2005) Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav Immun 19(5):389–397PubMedCrossRefGoogle Scholar
  39. Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Timmerman KL, McFarlin BK, Coen PM, Talbert E (2007) The influence of exercise training on inflammatory cytokines and C-reactive protein. Med Sci Sports Exerc 39(10):1714–1719. doi: 10.1249/mss.0b013e31811ece1c PubMedCrossRefGoogle Scholar
  40. Timmerman K, Flynn M, Coen P, Markofski M, Pence B (2008) Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise? J Leukoc Biol 84(5):1271–1278PubMedCrossRefGoogle Scholar
  41. Ulrich C, Heine GH, Gerhart MK, Kohler H, Girndt M (2008) Proinflammatory CD14+CD16+ monocytes are associated with subclinical atherosclerosis in renal transplant patients. Am J Transplant 8(1):103–110. doi: 10.1111/j.1600-6143.2007.02035.x PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Melissa M. Markofski
    • 1
  • Michael G. Flynn
    • 2
  • Andres E. Carrillo
    • 3
  • Cheryl L. H. Armstrong
    • 4
  • Wayne W. Campbell
    • 4
  • Darlene A. Sedlock
    • 5
  1. 1.Sealy Center on Aging, University of Texas Medical Branch at GalvestonGalvestonUSA
  2. 2.Department of Health and Human PerformanceCollege of CharlestonCharlestonUSA
  3. 3.Department of Exercise ScienceChatham UniversityPittsburghUSA
  4. 4.Department of Nutrition SciencePurdue UniversityWest LafayetteUSA
  5. 5.Department of Health and KinesiologyPurdue UniversityWest LafayetteUSA

Personalised recommendations