1. bookVolume 72 (2022): Issue 1 (March 2022)
Journal Details
First Published
25 Mar 2014
Publication timeframe
4 times per year
access type Open Access

Evaluation of Serum Iron and Ferritin Levels as Inflammatory Markers in Calves with Bovine Respiratory Disease Complex

Published Online: 05 Apr 2022
Volume & Issue: Volume 72 (2022) - Issue 1 (March 2022)
Page range: 59 - 75
Received: 26 Nov 2021
Accepted: 09 Feb 2022
Journal Details
First Published
25 Mar 2014
Publication timeframe
4 times per year

Iron and ferritin have been used in human medicine for years to reveal the presence of inflammation. However, studies evaluating these parameters, especially in respiratory system diseases, are quite rare in veterinary medicine. We aimed to test the usability of serum Fe and Fe-related parameters [total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC) and transferrin saturation (TS) levels] as inflammatory and diagnostic biomarkers in calves with bovine respiratory disease complex (BRDC). To mark inflammation, some selected acute-phase proteins including serum ferritin and transferrin levels were measured because of their close relationship with iron metabolism. The material of this study consisted of 15 calves, aged 1-3 months with BRDC (Group I) and 10 healthy calves aged 1-3 months (Group II) based on the presence of respiratory clinical findings. Serum Fe, TIBC and TS levels were low and ferritin levels were high in Group I (P ≤ 0.001). The BRDC group was separated into two subgroups based on PCR results, namely Virus+ (n=9) and Virus- (n=6). The calves in the Virus+ group had significantly lower levels of Fe (P=0.001) and significantly higher values of ferritin (P=0.002), compared to the healthy group. On the basis of inter-group comparison and ROC analysis, we concluded that Fe (primarily), ferritin, TIBC and TS levels can be used as inflammatory biomarkers and possible diagnostic markers in the BRDC as useful, practical, inexpensive substitutes. As a suggestion, these parameters which are believed to play a role in the pathogenesis of the disease, can be used as potential prognostic biomarkers in studies involving treatment.


1. Ceciliani F, Ceron JJ, Eckersall PD, Sauerwein H: Acute phase proteins in ruminants. J Proteomics 2012, 75:4207-4231.10.1016/j.jprot.2012.04.004 Search in Google Scholar

2. Petersen HH, Nielsen JP, Heegaard PM: Application of acute phase protein measurements in veterinary clinical chemistry. Vet Res 2004, 35:163-187.10.1051/vetres:2004002 Search in Google Scholar

3. Murata H, Shimada N, Yoshioka M: Current research on acute phase proteins in veterinary diagnosis: an overview. Vet J 2004, 168:28-40.10.1016/S1090-0233(03)00119-9 Search in Google Scholar

4. Baydar E, Dabak M. Serum iron as an indicator of acute inflammation in cattle. J. Dairy Sci 2014, 97:222-228.10.3168/jds.2013-693924268402 Search in Google Scholar

5. Orino K, Watanabe K: Molecular, physiological and clinical aspects of the iron storage protein ferritin. Vet J 2008, 178:191-201.10.1016/j.tvjl.2007.07.00617764995 Search in Google Scholar

6. Welsh RD, Dye LB, Payton ME, Confer AW: Isolation and antimicrobial susceptibilities of bacterial pathogens from bovine pneumonia: 1994--2002. J Vet Diagn Invest 2004, 16:426-431.10.1177/10406387040160051015460326 Search in Google Scholar

7. Snowder GD, Van Vleck LD, Cundiff LV, Bennett GL: Bovine respiratory disease in feedlot cattle: environmental, genetic, and economic factors. J Anim Sci 2006, 84:1999-2008.10.2527/jas.2006-04616864858 Search in Google Scholar

8. Valarcher JF, Taylor G: Bovine respiratory syncytial virus infection. Vet Res 2007, 38:153-180.10.1051/vetres:2006053 Search in Google Scholar

9. Jones C, Chowdhury S: A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex and development of improved vaccines. Anim Health Res Rev 2007, 8:187-205.10.1017/S146625230700134X18218160 Search in Google Scholar

10. Ellis JA: Update on viral pathogenesis in BRD. Anim Health Res Rev 2009, 10:149-153.10.1017/S146625230999020X20003652 Search in Google Scholar

11. Divers TJ: Respiratory diseases. In: Divers TJ, Peek SF, editors. Rebhun’s Diseases of Dairy Cattle. 2 nd ed. St. Louis, Missouri: Saunders; 2008, 79-127.10.1016/B978-141603137-6.50007-7 Search in Google Scholar

12. Ong ST, Ho JZ, Ho B, Ding JL: Iron-withholding strategy in innate immunity. Immunobiology 2006, 211:295-314.10.1016/j.imbio.2006.02.00416697921 Search in Google Scholar

13. Beard JL: Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 2001, 131:568-579.10.1093/jn/131.2.568S11160590 Search in Google Scholar

14. Aydoğdu U, Coșkun A, Yıldız R, Güzelbekteș H, Șen İ: Changes of hematological parameters and serum iron levels in calves with systemic inflamatory response syndrome. Eurasian J Vet Sci 2018, 34:56-59.10.15312/EurasianJVetSci.2018.180 Search in Google Scholar

15. Borges AS, Divers TJ, Stokol T, Mohammed OH: Serum iron and plasma fibrinogen concentrations as indicators of systemic inflammatory diseases in horses. J Vet Intern Med 2007, 21:489-494.10.1111/j.1939-1676.2007.tb02995.x Search in Google Scholar

16. Zandman-Goddard G, Shoenfeld Y: Ferritin in autoimmune diseases. Autoimmun Rev 2007, 6:457-463.10.1016/j.autrev.2007.01.01617643933 Search in Google Scholar

17. Ganz T, Nemeth E: Iron sequestration and anemia of inflammation. Semin Hematol 2009, 46:387-393.10.1053/j.seminhematol.2009.06.001275559119786207 Search in Google Scholar

18. Hintze KJ, Theil EC: Cellular regulation and molecular interactions of the ferritins. Cell Mol Life Sci 2006, 63:591-600.10.1007/s00018-005-5285-y16465450 Search in Google Scholar

19. Weinberg ED, Miklossy J: Iron withholding: a defense against disease. J Alzheimers Dis 2008, 13:451-463.10.3233/JAD-2008-13409 Search in Google Scholar

20. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T: IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004, 113:1271-1276.10.1172/JCI200420945 Search in Google Scholar

21. Neumann S: Serum iron level as an indicator for inflammation in dogs and cats. Comp Clin Path 2003, 12:90-94.10.1007/s00580-003-0481-3 Search in Google Scholar

22. Tsukano K, Fukuda T, Ikeda K, Sato K, Suzuki K: Serum iron concentration is candidate inflammatory marker for respiratory diseases in beef cows. J Vet Med Sci 2021, 83:824-828.10.1292/jvms.21-0051 Search in Google Scholar

23. Zhang C: Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell 2014, 5:750-760.10.1007/s13238-014-0083-7 Search in Google Scholar

24. Miyata Y, Furugouri K, Shijimaya K: Developmental changes in serum ferritin concentration of dairy calves. J Dairy Sci 1984, 67:1256-1263.10.3168/jds.S0022-0302(84)81432-0 Search in Google Scholar

25. Furugouri K, Miyata Y, Shijimaya K: Ferritin in blood serum of dairy cows. J Dairy Sci 1982, 65:1529-1534.10.3168/jds.S0022-0302(82)82377-1 Search in Google Scholar

26. Furugouri K, Miyata Y, Shijimaya K, Narasaki N: Developmental changes in serum ferritin of piglets. J Anim Sci 1983, 57:960-965.10.2527/jas1983.574960x6643308 Search in Google Scholar

27. Jacobs A, Miller F, Worwood M, Beamish MR, Wardrop CA: Ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. Br Med J 1972, 4:206-208.10.1136/bmj.4.5834.20617864815082548 Search in Google Scholar

28. Lorier MA, Herron JL, Carrell RW: Detecting iron deficiency by serum tests. Clin Chem 1985, 31:337-338.10.1093/clinchem/31.2.337 Search in Google Scholar

29. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV: Serum ferritin: Past, present and future. Biochim Biophys Acta 2010, 1800:760-769.10.1016/j.bbagen.2010.03.011289323620304033 Search in Google Scholar

30. Jacobs A, Worwood M: Ferritin in serum. Clinical and biochemical implications. N Engl J Med 1975, 292:951-956.10.1056/NEJM1975050129218051090831 Search in Google Scholar

31. Orino K: Biochemical studies on bovine ferritin. Jpn J Vet Res 1998, 46:96-97. Search in Google Scholar

32. Gomme PT, McCann KB, Bertolini J: Transferrin: structure, function and potential therapeutic actions. Drug Discov Today 2005, 10:267-273.10.1016/S1359-6446(04)03333-1 Search in Google Scholar

33. Koc M, Taysi S, Sezen O, Bakan N: Levels of some acute-phase proteins in the serum of patients with cancer during radiotherapy. Biol Pharm Bull 2003, 26:1494-1497.10.1248/bpb.26.149414519962 Search in Google Scholar

34. Graziadei I, Kaserbacher R, Braunsteiner H, Vogel W: The hepatic acute-phase proteins alpha 1-antitrypsin and alpha 2-macroglobulin inhibit binding of transferrin to its receptor. Biochem J 1993, 290:109-113.10.1042/bj290010911323887679893 Search in Google Scholar

35. Faruqi A, Mukkamalla SKR. Iron Binding Capacity. StatPearls. Treasure Island (FL)2020. Search in Google Scholar

36. Hunter JE: Variable effects of iron status on the concentration of ferritin in rat plasma, liver, and spleen. J Nutr 1978, 108 (3):497-505.10.1093/jn/108.3.497627922 Search in Google Scholar

37. Li JY, Paragas N, Ned RM, Qiu A, Viltard M, Leete T, Drexler IR, Chen X, Sanna-Cherchi S, Mohammed F, Williams D, Lin CS, Schmidt-Ott KM, Andrews NC, Barasch J: Scara5 is a ferritin receptor mediating non-transferrin iron delivery. Dev Cell 2009,16:35-46.10.1016/j.devcel.2008.12.002265250319154717 Search in Google Scholar

38. Elsayed ME, Sharif MU, Stack AG: Transferrin saturation: a body iron biomarker. Adv Clin Chem 2016, 75:71-97.10.1016/bs.acc.2016.03.00227346617 Search in Google Scholar

39. Gozzelino R, Arosio P: Iron homeostasis in health and disease. Int J Mol Sci 2016, 17:130.10.3390/ijms17010130473037126805813 Search in Google Scholar

40. Kirbas A, Kandemir FM, Celebi D, Hanedan B, Timurkan MO: The use of inflammatory markers as a diagnostic and prognostic approach in neonatal calves with septicaemia. Acta Vet Hung 2019, 67:360-376.10.1556/004.2019.03731549538 Search in Google Scholar

41. Tsukano K, Shimamori T, Suzuki K: Serum iron concentration in cattle with endotoxaemia. Acta Vet Hung 2020, 68:53-58.10.1556/004.2020.0001632384071 Search in Google Scholar

42. Aydoğdu U, Yurdakul İ: The effects of local and systemic inflammatory status on iron metabolism and lipid profile in calves. Eurasian J Vet Sci 2020, 36:121-126.10.15312/EurasianJVetSci.2020.269 Search in Google Scholar

43. Ali MK, Kim RY, Karim R, Mayall JR, Martin KL, Shahandeh A, Abbasian F, Starkey MR, Loustaud-Ratti V, Johnstone D, Milward EA, Hansbro PM, Horvat JC: Role of iron in the pathogenesis of respiratory disease. Int J Biochem Cell Biol 2017, 88:181-195.10.1016/j.biocel.2017.05.003 Search in Google Scholar

44. Šoltésová H, Nagyová V, Tóthová C, Nagy O: Haematological and blood biochemical alterations associated with respiratory disease in calves. Acta Vet Brno 2015, 84:249-256.10.2754/avb201584030249 Search in Google Scholar

45. Seitz WR: Immunoassay labels based on chemiluminescence and bioluminescence. Clin Biochem 1984, 17:120-125.10.1016/S0009-9120(84)90318-7 Search in Google Scholar

46. Timurkan MO, Aydin H: Increased genetic diversity of BVDV strains circulating in Eastern Anatolia, Turkey: first detection of BVDV-3 in Turkey. Trop Anim Health Prod 2019, 51:1953-1961.10.1007/s11250-019-01901-631055737 Search in Google Scholar

47. Timurkan MO, Aydin H, Sait A: Identification and molecular characterisation of Bovine Parainfluenza Virus-3 and Bovine Respiratory Syncytial Virus - first report from Turkey. J Vet Res 2019, 63:167-173.10.2478/jvetres-2019-0022659818331276055 Search in Google Scholar

48. Fuchs M, Hü bert P, Detterer J, Rziha HJ: Detection of bovine herpesvirus type 1 in blood from naturally infected cattle by using a sensitive PCR that discriminates between wild-type virus and virus lacking glycoprotein E. J Clin Microbiol 1999, 37:2498-2507.10.1128/JCM.37.8.2498-2507.19998526810405392 Search in Google Scholar

49. Kaneko JJ. Iron metabolism. In: Clinical biochemistry of domestic animals. New York: Academic press; 1980, 649–669.10.1016/B978-0-12-396350-5.50021-8 Search in Google Scholar

50. Kirchhoff J, Uhlenbruck S, Goris K, Keil GM, Herrler G: Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection. Vet Res 2014, 45:20.10.1186/1297-9716-45-20394211424548739 Search in Google Scholar

51. Dörtkardeş AB, Şahinduran Ş: Determination of serum amyloid A, haptoglobin and hepcidin levels in calves with endemic viral pneumonia. Ankara Üniv Vet Fak Derg 2020, 67:127-131.10.33988/auvfd.523958 Search in Google Scholar

52. Gökçe G: Investigations on Clinic,Haematology,Biochemistry,Oxidative Stress, Acute Phase Proteins in Infectious Respiratory Disease Complex (BRDC) in Cattle. Ataturk Univ Vet Bil Derg 2017, 12:34-44. Search in Google Scholar

53. Hanedan B, Kirbas A, Dorman E, Timurkan MO, Kandemir FM, Alkan O: Cardiac troponin-i concentration in weaned calves with bovine respiratory disease. Acta Vet-Beograd 2015, 65:454-462.10.1515/acve-2015-0038 Search in Google Scholar

54. Wesselius LJ, Nelson ME, Skikne BS: Increased release of ferritin and iron by iron-loaded alveolar macrophages in cigarette smokers. Am J Respir Crit Care Med 1994, 150:690-695.10.1164/ajrccm.150.3.8087339 Search in Google Scholar

55. Yaman T, Büyükbayram H, Özyıldız Z, Terzi F, Uyar A, Keles ÖF, Özsoy ŞY, Yener Z: Detection of Bovine Respiratory Syncytial Virus, Pasteurella Multocida, and Mannheimia Haemolytica by Immunohistochemical Method in Naturally-infected Cattle. J Vet Res 2018, 62:439-445.10.2478/jvetres-2018-0070 Search in Google Scholar

56. Fulton RW, Purdy CW, Confer AW, Saliki JT, Loan RW, Briggs RE, Burge LJ: Bovine viral diarrhea viral infections in feeder calves with respiratory disease: interactions with Pasteurella spp., parainfluenza-3 virus, and bovine respiratory syncytial virus. Can J Vet Res 2000, 64:151-159. Search in Google Scholar

57. Ward CG, Bullen JJ, Rogers HJ: Iron and infection: New developments and their implications. J Trauma 1996, 41:356-364.10.1097/00005373-199608000-00030 Search in Google Scholar

58. Tsukano K, Shimamori T, Fukuda T, Nishi Y, Otsuka M, Kitade Y, Suzuki K: Serum iron concentration as a marker of inflammation in young cows that underwent dehorning operation. J Vet Med Sci 2019, 81:626-628.10.1292/jvms.19-0002 Search in Google Scholar

59. Jacobsen S, Nielsen JV, Kjelgaard-Hansen M, Toelboell T, Fjeldborg J, Halling-Thomsen M, Martinussen T, Thoefner MB: Acute phase response to surgery of varying intensity in horses: a preliminary study. Vet Surg 2009, 38:762-769.10.1111/j.1532-950X.2009.00564.x Search in Google Scholar

60. Olivares M, Walter T, Osorio M, Chadud P, Schlesinger L. Anemia of a mild viral-infection - the measles-vaccine as a model. Pediatrics 1989, 84:851-855.10.1542/peds.84.5.851 Search in Google Scholar

61. Drakesmith H, Prentice A: Viral infection and iron metabolism. Nat Rev Microbiol 2008, 6:541-52.10.1038/nrmicro1930 Search in Google Scholar

62. Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S: Serum iron level as a potential predictor of coronavirus disease 2019 severity and mortality: a retrospective study. Open Forum Infect Dis 2020, 7:ofaa250.10.1093/ofid/ofaa250 Search in Google Scholar

63. Schnell SA, Ohtsuka H, Kakinuma S, Yoshikawa Y, Watanabe K, Orino K: Iron and ferritin levels in the serum and milk of bovine leukemia virus-infected dairy cows. Front Vet Sci 2015, 2:12.10.3389/fvets.2015.00012 Search in Google Scholar

64. Payne SM: Iron acquisition in microbial pathogenesis. Trends Microbiol 1993, 1:66-69.10.1016/0966-842X(93)90036-Q Search in Google Scholar

65. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003, 101:2461-2463.10.1182/blood-2002-10-323512433676 Search in Google Scholar

66. Potgieter LN, McCracken MD, Hopkins FM, Walker RD: Effect of bovine viral diarrhea virus infection on the distribution of infectious bovine rhinotracheitis virus in calves. Am J Vet Res 1984, 45:687-90. Search in Google Scholar

67. Yaman, T and Aydemir, C: Respiratory Syncytial Virus Infection Induces Expression of Inducible Nitric Oxide Synthase, CD3, and CD8 in Naturally Occurring Pneumonia in Lambs. Acta Vet-Beograd 2021, 71:170-188.10.2478/acve-2021-0015 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo