Skip to main content
SpringerLink
Log in

Serum interleukin 6 could be a valuable initial diagnostic tool in prosthetic knee joint infections

  • Original Article • KNEE - INFECTION
  • Published:
European Journal of Orthopaedic Surgery & Traumatology Aims and scope Submit manuscript

Abstract

Background

Accurate preoperative diagnosis of prosthetic joint infection (PJI) in the absence of obvious clinical signs or laboratory findings is challenging. Interleukin 6 (IL-6) has been proposed as an infection marker but supportive data are limited. We studied the diagnostic utility of serum IL-6 in infected total knee arthroplasty (TKA).

Methods

A prospective cohort study was done in 52 patients (59 knees) with a painful TKA. The abnormal limits for serum IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), synovial fluid white cell counts (WBC) and synovial fluid neutrophils (PMN) were determined from receiver operating characteristic curves. An infection was defined as the presence of sinus tract or positive culture > two separate tissue or fluid samples. We utilized Mann–Whitney test, Spearman’s correlation and Fischer’s exact test to determine the sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of serum IL-6.

Results

The optimal threshold concentration of serum IL-6 was 9.14 pg/ml. Independently, this yielded a sensitivity, specificity and NPV of 81%, 63% and 85%, respectively, and when combined with synovial fluid WBC, values were 100%, 90%, 100%, respectively. The sensitivity and specificity of ESR (70%, 63.6%), CRP (66.7%, 66.7%), synovial WBC (66.7%, 81%) and synovial PMN (82.4%, 73.7%) were also calculated. Serum IL-6 levels strongly correlate with all markers in PJI.

Conclusions

Serum IL-6 improves the diagnosis of PJI over existing methods, especially when combined with synovial fluid WBC. Its optimal usage is as an excellent screening test to rule out infected total knee arthroplasty.

Level of Evidence

Diagnostic Level II.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Choe H, Deirmengian CA, Hickok NJ, Morrison TN, Tuan RS (2015) Molecular diagnostics. J Am Acad Orthop Surg 23(Suppl):S26–S31. https://doi.org/10.5435/JAAOS-D-14-00409

    Article  PubMed  PubMed Central  Google Scholar 

  2. Peersman G, Laskin R, Davis J, Peterson M (2001) Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop Relat Res 392:15–23

    Article  Google Scholar 

  3. Abdel MP, Akgun D, Akin G, Akinola B, Alencar P, Amanatullah DF, Babazadeh S, Borens O, Vicente Cabral RM, Cichos KH, Deirmengian C, de Steiger R, Ghanem E, Radtke Goncalves JR, Goodman S, Hamlin B, Hwang K, Klatt BA, Lee GC, Manrique J, Moon AS, Ogedegbe F, Salib CG, Tian S, Winkler T (2019) Hip and knee section, diagnosis, pathogen isolation, culture: proceedings of international consensus on orthopedic infections. J Arthroplasty 34(2S):S361–S367. https://doi.org/10.1016/j.arth.2018.09.020

    Article  PubMed  Google Scholar 

  4. Kubista B, Hartzler RU, Wood CM, Osmon DR, Hanssen AD, Lewallen DG (2012) Reinfection after two-stage revision for periprosthetic infection of total knee arthroplasty. Int Orthop 36(1):65–71. https://doi.org/10.1007/s00264-011-1267-x

    Article  PubMed  Google Scholar 

  5. Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N (2018) The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty 33(5):1309–1314. https://doi.org/10.1016/j.arth.2018.02.078

    Article  PubMed  Google Scholar 

  6. Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N (1999) Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol 37(10):3281–3290

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Berbari E, Mabry T, Tsaras G, Spangehl M, Erwin PJ, Murad MH, Steckelberg J, Osmon D (2010) Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis. J Bone Joint Surg Am 92(11):2102–2109. https://doi.org/10.2106/JBJS.I.01199

    Article  PubMed  Google Scholar 

  8. Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C (2007) Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br 89(1):94–99. https://doi.org/10.1302/0301-620X.89B1.17485

    Article  CAS  PubMed  Google Scholar 

  9. Buttaro MA, Tanoira I, Comba F, Piccaluga F (2010) Combining C-reactive protein and interleukin-6 may be useful to detect periprosthetic hip infection. Clin Orthop Relat Res 468(12):3263–3267. https://doi.org/10.1007/s11999-010-1451-0

    Article  PubMed  PubMed Central  Google Scholar 

  10. Di Cesare PE, Chang E, Preston CF, Liu CJ (2005) Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am 87(9):1921–1927. https://doi.org/10.2106/JBJS.D.01803

    Article  PubMed  Google Scholar 

  11. Mitchell D, Perez J, Grau L, Summers S, Rosas S, Ong A, Schneiderbauer MM, Hernandez VH (2017) Systematic review of novel synovial fluid markers and polymerase chain reaction in the diagnosis of prosthetic joint infection. Am J Orthop (Belle Mead NJ) 46(4):190–198

    Google Scholar 

  12. Jacovides CL, Parvizi J, Adeli B, Jung KA (2011) Molecular markers for diagnosis of periprosthetic joint infection. J Arthroplasty 26(6 Suppl):99–103. https://doi.org/10.1016/j.arth.2011.03.025

    Article  PubMed  Google Scholar 

  13. Deirmengian CA, Liang L, Rosenberger JP, Joaquim TR, Gould MR, Citrano PA, Kardos KW (2018) The leukocyte esterase test strip is a poor rule-out test for periprosthetic joint infection. J Arthroplasty 33(8):2571–2574. https://doi.org/10.1016/j.arth.2018.03.005

    Article  PubMed  Google Scholar 

  14. Aggarwal VK, Higuera C, Deirmengian G, Parvizi J, Austin MS (2013) Swab cultures are not as effective as tissue cultures for diagnosis of periprosthetic joint infection. Clin Orthop Relat Res 471(10):3196–3203. https://doi.org/10.1007/s11999-013-2974-y

    Article  PubMed  PubMed Central  Google Scholar 

  15. Deirmengian CA, Citrano PA, Gulati S, Kazarian ER, Stave JW, Kardos KW (2016) The C-reactive protein may not detect infections caused by less-virulent organisms. J Arthroplasty 31(9 Suppl):152–155. https://doi.org/10.1016/j.arth.2016.01.060

    Article  PubMed  Google Scholar 

  16. Bonanzinga T, Ferrari MC, Tanzi G, Vandenbulcke F, Zahar A, Marcacci M (2019) The role of alpha defensin in prosthetic joint infection (PJI) diagnosis: a literature review. EFORT Open Rev 4(1):10–13. https://doi.org/10.1302/2058-5241.4.180029

    Article  PubMed  PubMed Central  Google Scholar 

  17. Honda M, Kitamura K, Mizutani Y, Oishi M, Arai M, Okura T, Igarahi K, Yasukawa K, Hirano T, Kishimoto T et al (1990) Quantitative analysis of serum IL-6 and its correlation with increased levels of serum IL-2R in HIV-induced diseases. J Immunol 145(12):4059–4064

    CAS  PubMed  Google Scholar 

  18. Wirtz DC, Heller KD, Miltner O, Zilkens KW, Wolff JM (2000) Interleukin-6: a potential inflammatory marker after total joint replacement. Int Orthop 24(4):194–196. https://doi.org/10.1007/s002640000136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sakamoto K, Arakawa H, Mita S, Ishiko T, Ikei S, Egami H, Hisano S, Ogawa M (1994) Elevation of circulating interleukin 6 after surgery: factors influencing the serum level. Cytokine 6(2):181–186

    Article  CAS  Google Scholar 

  20. Deirmengian C, Lonner JH, Booth RE Jr (2005) The Mark Coventry award: white blood cell gene expression: a new approach toward the study and diagnosis of infection. Clin Orthop Relat Res 440:38–44. https://doi.org/10.1097/01.blo.0000185756.17401.32

    Article  PubMed  Google Scholar 

  21. Peel TN, Dylla BL, Hughes JG, Lynch DT, Greenwood-Quaintance KE, Cheng AC, Mandrekar JN, Patel R (2016) Improved diagnosis of prosthetic joint infection by culturing periprosthetic tissue specimens in blood culture bottles. MBio 7(1):e01776-01715. https://doi.org/10.1128/mBio.01776-15

    Article  CAS  Google Scholar 

  22. Rak M, Barlic-Maganja D, Kavcic M, Trebse R, Cor A (2013) Comparison of molecular and culture method in diagnosis of prosthetic joint infection. FEMS Microbiol Lett 343(1):42–48. https://doi.org/10.1111/1574-6968.12125

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funds were received in support of this study.

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Central Arkansas Veterans Healthcare System, University of Arkansas College of Medicine, 4300 West 7th St, Little Rock, AR, 72205, USA

    Isaac Majors & Vivek S. Jagadale

Authors
  1. Isaac Majors
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vivek S. Jagadale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vivek S. Jagadale.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Appendices

Appendix 1

See Fig. 2.

Fig. 2
figure 2

Musculoskeletal infection society (MSIS) definition for the diagnosis of prosthetic joint infection (PJI)

Full size image

Appendix 2

See Table 7.

Table 7 95% confidence interval values for Table 1
Full size table

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Majors, I., Jagadale, V.S. Serum interleukin 6 could be a valuable initial diagnostic tool in prosthetic knee joint infections. Eur J Orthop Surg Traumatol 29, 1781–1788 (2019). https://doi.org/10.1007/s00590-019-02519-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00590-019-02519-y

Keywords

Search

Navigation