Tierarztl Prax Ausg G Grosstiere Nutztiere 2024; 52(01): 33-41
DOI: 10.1055/a-2241-7556

Haptoglobin als Indikator für Erkrankungen in der Frühlaktation von Milchkühen unter besonderer Berücksichtigung der Eutergesundheit

Haptoglobin as an indicator for diseases during early lactation of dairy cows, with particular consideration of udder health
Sarah Plattner
1   Klinik für Wiederkäuer mit Ambulanz und Bestandsbetreuung, Ludwig-Maximilians-Universität München
Rolf Mansfeld
1   Klinik für Wiederkäuer mit Ambulanz und Bestandsbetreuung, Ludwig-Maximilians-Universität München
› Author Affiliations


Haptoglobin (HP) ist als Akute-Phase-Protein Teil der unspezifischen Immunantwort und stellt einen aussagekräftigen Indikator für Entzündungszustände beim Rind dar. Die vorliegende Arbeit soll einen Überblick über bisherige Studienergebnisse zu Serum- und Milch-HP in Zusammenhang mit Erkrankungen in der Frühlaktation unter besonderer Berücksichtigung der Eutergesundheit geben. Bei entzündlichen Erkrankungen des Reproduktionstraktes, des Stoffwechsels und des Bewegungsapparates steigt HP im Blutserum an und kann als unspezifischer Indikator für Erkrankungen in der Frühlaktation dienen. Für die Differenzierung von gesunden und kranken Tieren stehen Grenzwerte zur Verfügung. Es besteht eine Korrelation zwischen HP in Blut und Milch. Die HP-Konzentration in Milch wird nicht nur von systemischen Erkrankungen beeinflusst, sondern das Euterepithel ist im Fall einer Infektion auch selbst in der Lage, HP zu synthetisieren. Bei Mastitis kann anhand der HP-Konzentration auf die Schwere der Erkrankung rückgeschlossen werden. Außerdem liefert die Höhe des HP-Anstiegs in Milch Hinweise auf das verursachende Pathogen. Für die Differenzierung von gesunden und subklinisch bzw. klinisch erkrankten Tieren stehen Grenzwerte für Milch-HP zur Verfügung.


s an acute-phase protein Haptoglobin (HP) is part of the non-specific immune response and represents a strong indicator for inflammatory conditions in cattle. The purpose of this article is to provide an overview of previous study results on serum and milk HP related to diseases in early lactation with special consideration of udder health. During inflammatory diseases of the reproductive tract, metabolism and musculoskeletal system, HP increases in the serum and may serve as a non-specific indicator for diseases during early lactation. Threshold values are available for the differentiation of healthy from diseased animals. A correlation exists between HP in blood and milk. The HP concentration in milk is not only influenced by systemic disorders, as the udder epithelium is also independently capable of synthesizing HP in case of an infection. In mastitis, HP concentration may be used to estimate the severity of the disease. In addition, HP may provide certain suspicions regarding the causative pathogen. Threshold values for milk HP are available for the differentiation of healthy individuals from subclinically resp. clinically affected animals.

Publication History

Received: 06 July 2023

Accepted: 13 November 2023

Article published online:
27 February 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • Literatur

  • 1 Horadagoda NU, Knox KM, Gibbs HA. et al. Acute phase proteins in cattle: discrimination between acute and chronic inflammation. Vet Rec 1999; 144: 437-441 DOI: 10.1136/vr.144.16.437.
  • 2 Jain S, Gautam V, Naseem S. Acute-phase proteins: As diagnostic tool. J Pharm Bioallied Sci 2011; 3: 118
  • 3 Abernethy TJ, Avery OT. The occurence during acute infections of a protein not normally present in the blood : I. Distribution of the protein in patient̓s sera and the effect of calcium on the flocculation reaction with c polysaccharide of pneumococcus. J Exp Med 1941; 73: 173-182 DOI: 10.1084/jem.73.2.173.
  • 4 Ceciliani F, Ceron JJ, Eckersall PD. et al. Acute phase proteins in ruminants. J Proteomics 2012; 75: 4207-4231 DOI: 10.1016/j.jprot.2012.04.004.
  • 5 Koj A. Initiation of acute phase response and synthesis of cytokines. Biochim Biophys Acta Mol Basis Dis 1996; 1317: 84-94
  • 6 Gruys E, Toussaint MJ, Niewold TA. et al. Acute phase reaction and acute phase proteins. J Zhejiang Univ Sci B 2005; 6: 1045-1056 DOI: 10.1631/jzus.2005.B1045.
  • 7 Baumann H, Gauldie J. The acute phase response. Immunol Today 1994; 15: 74-80
  • 8 Dobryszycka W. Biological functions of haptoglobin-new pieces to an old puzzle. Eur J Clin Chem Clin Biochem 1997; 35: 647-654
  • 9 Tóthová C, Nagy O, Seidel H. et al. Acute phase proteins as markers of diseases in farm animals. Acute Phase Proteins as Early Non-Specific Biomarkers of Human and Veterinary Diseases 2011; 231-258
  • 10 Tóthová C, Nagy O, Kovac G. Acute phase proteins and their use in the diagnosis of diseases in ruminants: a review. Vet Med (Praha) 2014; 59: 163-180 DOI: 10.17221/7478-vetmed.
  • 11 Eckersall P. Acute phase proteins as markers of inflammatory lesions. Comparative Haematology International 1995; 5: 93-97
  • 12 Murata H, Shimada N, Yoshioka M. Current research on acute phase proteins in veterinary diagnosis: an overview. Vet J 2004; 168: 28-40
  • 13 Eckersall P, Conner J. Bovine and canine acute phase proteins. Vet Res Commun 1988; 12: 169-178
  • 14 Petersen HH, Nielsen JP, Heegaard PMH. Application of acute phase protein measurements in veterinary clinical chemistry. Vet Res 2004; 35: 163-187
  • 15 Eckersall P, Bell R. Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. Vet J 2010; 185: 23-27
  • 16 Young C, Eckersall P, Saini P. et al. Validation of immunoassays for bovine haptoglobin. Vet Immunol Immunopathol 1995; 49: 1-13
  • 17 Huzzey J, Duffield T, LeBlanc S. et al. Haptoglobin as an early indicator of metritis. J Dairy Sci 2009; 92: 621-625
  • 18 Hajek F, Reus A, Gruber S. et al. Use of serum haptoglobin concentration as an indicator in animal health monitoring of dairy cows. Tierarztl Prax Ausg G Grosstiere Nutztiere 2020; 48: 228-238
  • 19 Alberghina D, Piccione G, Casella S. et al. The effect of the season on some blood metabolites and haptoglobin in dairy cows during postpartum period. Arch Anim Breed. 2013; 56: 354-359
  • 20 Chan JPW, Chu CC, Fung HP. et al. Serum haptoglobin concentration in cattle. J Vet Med Sci 2004; 66: 43-46 DOI: 10.1292/jvms.66.43.
  • 21 Lomborg S, Nielsen L, Heegaard PM. et al. Acute phase proteins in cattle after exposure to complex stress. Vet Res Commun 2008; 32: 575-582
  • 22 Uchida E, Katoh N, Takahashi K. Appearance of Haptoglobin in Serum From Cows at Parturition. J Vet Med Sci 1993; 55: 893-894
  • 23 Debski B, Nowicki T, Zalewski W. et al. Evaluation of acute phase proteins in clinically healthy dairy cows in perinatal period and during lactation. Pol J Vet Sci 2016; 19: 519-523 DOI: 10.1515/pjvs-2016-0065.
  • 24 Arfuso F, Minuti A, Liotta L. et al. Stress and inflammatory response of cows and their calves during peripartum and early neonatal period. Theriogenology 2023; 196: 157-166
  • 25 Humblet MF, Guyot H, Boudry B. et al. Relationship between haptoglobin, serum amyloid A, and clinical status in a survey of dairy herds during a 6-month period. Vet Clin Pathol 2006; 35: 188-193
  • 26 Sheldon I, Noakes D, Rycroft A. et al. Acute phase protein responses to uterine bacterial contamination in caftle after calving. Vet Rec 2001; 148: 172-175
  • 27 Chan JPW, Chang CC, Hsu WL. et al. Association of increased serum acute-phase protein concentrations with reproductive performance in dairy cows with postpartum metritis. Vet Clin Pathol 2010; 39: 72-78
  • 28 Barragan A, Piñeiro J, Schuenemann G. et al. Assessment of daily activity patterns and biomarkers of pain, inflammation, and stress in lactating dairy cows diagnosed with clinical metritis. J Dairy Sci 2018; 101: 8248-8258
  • 29 Burfeind O, Sannmann I, Voigtsberger R. et al. Receiver operating characteristic curve analysis to determine the diagnostic performance of serum haptoglobin concentration for the diagnosis of acute puerperal metritis in dairy cows. Anim Reprod Sci 2014; 149: 145-151 DOI: 10.1016/j.anireprosci.2014.07.020.
  • 30 Pohl A, Burfeind O, Heuwieser W. The associations between postpartum serum haptoglobin concentration and metabolic status, calving difficulties, retained fetal membranes, and metritis. J Dairy Sci 2015; 98: 4544-4551
  • 31 Brodzki P, Brodzki A, Krakowski L. et al. Levels of selected cytokines and acute-phase proteins in the serum of dairy cows with cystic ovarian disease and those in follicular and luteal phases of normal ovarian cycle. Res Vet Sci 2019; 123: 20-25 DOI: 10.1016/j.rvsc.2018.12.007.
  • 32 Brodzki P, Kostro K, Brodzki A. et al. Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum. Theriogenology 2015; 84: 11-18
  • 33 Brodzki P, Kostro K, Krakowski L. et al. Inflammatory cytokine and acute phase protein concentrations in the peripheral blood and uterine washings of cows with subclinical endometritis in the late postpartum period. Vet Res Commun 2015; 39: 143-149
  • 34 Dubuc J, Duffield T, Leslie K. et al. Risk factors for postpartum uterine diseases in dairy cows. J Dairy Sci 2010; 93: 5764-5771
  • 35 Shin D, Jeong J, Choi I. et al. Associations between serum haptoglobin concentration and peri-and postpartum disorders, milk yield, and reproductive performance in dairy cows. Livestock Science 2018; 213: 14-18
  • 36 Smith BI, Donovan GA, Risco CA. et al. Serum haptoglobin concentrations in Holstein dairy cattle with toxic puerperal metritis. Vet Rec 1998; 142: 83-85 DOI: 10.1136/vr.142.4.83.
  • 37 El-Deeb WM, Elmoslemany AM. Acute phase proteins as biomarkers of Urinary Tract Infection in dairy cows: diagnostic and prognostic accuracy. Jpn J Vet Res 2016; 64: 57-66
  • 38 El-Deeb WM, El-Bahr SM. Biomarkers of ketosis in dairy cows at postparturient period: acute phase proteins and pro-inflammatory cytokines. Vet Arhiv 2017; 87: 431-440 DOI: 10.24099/vet.arhiv.160126c.
  • 39 Abuajamieh M, Kvidera SK, Fernandez MVS. Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows. Res Vet Sci 2016; 109: 81-85
  • 40 Gozho G, Plaizier J, Krause D. et al. Subacute ruminal acidosis induces ruminal lipopolysaccharide endotoxin release and triggers an inflammatory response. J Dairy Sci 2005; 88: 1399-1403
  • 41 Ametaj BN, Bradford BJ, Bobe G. et al. Strong relationships between mediators of the acute phase response and fatty liver in dairy cows. Can J Anim Sci 2005; 85: 165-175 DOI: 10.4141/a04-043.
  • 42 Saremi B, Al-Dawood A, Winand S. et al. Bovine haptoglobin as an adipokine: Serum concentrations and tissue expression in dairy cows receiving a conjugated linoleic acids supplement throughout lactation. Vet Immunol Immunopathol 2012; 146: 201-211
  • 43 Maffei M, Barone I, Scabia G. et al. The multifaceted haptoglobin in the context of adipose tissue and metabolism. Endocr Rev 2016; 37: 403-416
  • 44 Tóthová C, Nagy O, Seidel H. et al. The influence of hoof diseases on the concentrations of some acute phase proteins and other variables of the protein profile in heifers. Acta Vet Brno 2011; 61: 141-150
  • 45 Bagga A, Randhawa SS, Sharma S. et al. Acute phase response in lame crossbred dairy cattle. Vet World 2016; 9: 1204-1208 DOI: 10.14202/vetworld.2016.1204-1208.
  • 46 Smith BI, Kauffold J, Sherman L. Serum haptoglobin concentrations in dairy cattle with lameness due to claw disorders. Vet J 2010; 186: 162-165 DOI: 10.1016/j.tvjl.2009.08.012.
  • 47 Nazifi S, Esmailnezhad Z, Haghkhah M. et al. Acute phase response in lame cattle with interdigital dermatitis. World J Microbiol Biotechnol 2012; 28: 1791-1796
  • 48 Tadich N, Tejeda C, Bastias S. et al. Nociceptive threshold, blood constituents and physiological values in 213 cows with locomotion scores ranging from normal to severely lame. Vet J 2013; 197: 401-405 DOI: 10.1016/j.tvjl.2013.01.029.
  • 49 Yang F, Friedrichs WE, Navarijo-Ashbaugh AL. et al. Cell type-specific and inflammatory-induced expression of haptoglobin gene in lung. Lab Invest 1995; 73: 433-440
  • 50 Friedrichs WE, Navarijoashbaugh AL, Bowman BH. et al. Expression and inflammatory regulation of haptoglobin gene in adipocytes. Biochem Biophys Res Commun 1995; 209: 250-256
  • 51 Eckersall PD, Young FJ, McComb C. et al. Acute phase proteins in serum and milk from dairy cows with clinical mastitis. Vet Rec 2001; 148: 35-41 DOI: 10.1136/vr.148.2.35.
  • 52 Kovac G, Popelkova M, Tkacikova L. et al. Interrelationship between somatic cell count and acute phase proteins in serum and milk of dairy cows. Acta Vet Brno 2007; 76: 51-57 DOI: 10.2754/avb200776010051.
  • 53 Nielsen BH, Jacobsen S, Andersen P. et al. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions. Vet Rec 2004; 154: 361-365
  • 54 Thielen M, Mielenz M, Hiss S. et al. Cellular localization of haptoglobin mRNA in the experimentally infected bovine mammary gland. J Dairy Sci 2007; 90: 1215-1219
  • 55 Whelehan CJ, Meade KG, Eckersall PD. et al. Experimental Staphylococcus aureus infection of the mammary gland induces region-specific changes in innate immune gene expression. Vet Immunol Immunopathol 2011; 140: 181-189
  • 56 Hiss S, Mielenz M, Bruckmaier RM. et al. Haptoglobin concentrations in blood and milk after endotoxin challenge and quantification of mammary Hp mRNA expression. J Dairy Sci 2004; 87: 3778-3784 DOI: 10.3168/jds.S0022-0302(04)73516-X.
  • 57 Lai I-H, Tsao JH, Lu YP. et al. Neutrophils as one of the major haptoglobin sources in mastitis affected milk. Vet Res 2009; 40: 1
  • 58 Åkerstedt M, Waller KP, Sternesjö Å. Haptoglobin and serum amyloid A in relation to the somatic cell count in quarter, cow composite and bulk tank milk samples. J Dairy Res 2007; 74: 198-203
  • 59 Grönlund U, Hultén C, Eckersall PD. et al. Haptoglobin and serum amyloid A in milk and serum during acute and chronic experimentally induced Staphylococcus aureus mastitis. J Dairy Res 2003; 70: 379
  • 60 Åkerstedt M, Forsbäck L, Larsen T. et al. Natural variation in biomarkers indicating mastitis in healthy cows. J Dairy Res 2011; 78: 88
  • 61 Thomas FC, Waterston M, Hastie P. et al. Early post parturient changes in milk acute phase proteins. J Dairy Res 2016; 83: 352-359 DOI: 10.1017/S0022029916000297.
  • 62 Wollowski L, Heuwieser W, Kossatz A. et al. The value of the biomarkers cathelicidin, milk amyloid A, and haptoglobin to diagnose and classify clinical and subclinical mastitis. J Dairy Sci 2021; 104: 2106-2122
  • 63 Thomas F, Geraghty T, Simões P. et al. A pilot study of acute phase proteins as indicators of bovine mastitis caused by different pathogens. Res Vet Sci 2018; 119: 176-181
  • 64 Pyörälä S, Hovinen M, Simojoki H. et al. Acute phase proteins in milk in naturally acquired bovine mastitis caused by different pathogens. Vet Rec 2011; 168: 535-535
  • 65 Thomas FC, Waterston M, Hastie P. et al. The major acute phase proteins of bovine milk in a commercial dairy herd. BMC Vet Res 2015; 11: 1-10
  • 66 Hiss S, Mueller U, Neu-Zahren A. et al. Haptoglobin and lactate dehydrogenase measurements in milk for the identification of subclinically diseased udder quarters. Vet Med (Praha) 2007; 52: 245
  • 67 Kalmus P, Simojoki H, Pyörälä S. et al. Milk haptoglobin, milk amyloid A, and N-acetyl-β-d-glucosaminidase activity in bovines with naturally occurring clinical mastitis diagnosed with a quantitative PCR test. J Dairy Sci 2013; 96: 3662-3670
  • 68 Pedersen L, Aalbaek B, Røntved C. et al. Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis. J Comp Pathol 2003; 128: 156-164
  • 69 Wenz JR, Fox L, Muller F. et al. Factors associated with concentrations of select cytokine and acute phase proteins in dairy cows with naturally occurring clinical mastitis. J Dairy Sci 2010; 93: 2458-2470
  • 70 Suojala L, Orro T, Järvinen H. et al. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows. Acta Vet Scand 2008; 50: 1-10
  • 71 Simões P, Campbell M, Viora L. et al. Pilot study into milk haptoglobin as an indicator of udder health in heifers after calving. Res Vet Sci 2018; 116: 83-87
  • 72 Eckersall P, Young F, Nolan A. et al. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis. J Dairy Sci 2006; 89: 1488-1501
  • 73 Rinaldi M, Li RW, Bannerman DD. et al. A sentinel function for teat tissues in dairy cows: dominant innate immune response elements define early response to E. coli mastitis. Funct Integr Genomics 2010; 10: 21-38 DOI: 10.1007/s10142-009-0133-z.
  • 74 Dalanezi FM, Schmidt E, Joaquim SF. et al. Concentrations of Acute-Phase Proteins in Milk from Cows with Clinical Mastitis Caused by Different Pathogens. Pathogens 2020; 9: 706
  • 75 Metzner M, Horber J, Rademacher G. et al. Application of the glutaraldehyde test in cattle. J Vet Med A 2007; 54: 449-454