Skip to main content

Low-dose intra-articular autologous conditioned serum in treatment of primary knee osteoarthritis



Interleukin-1 (IL-1) plays an important role in the pathogenesis of osteoarthritis. Hence, agents that inhibit such cytokine have a high therapeutic potential. A method of therapy depends on competitive inhibition of IL-1 at the receptor level – that is, IL-1 receptor antagonist; such antagonist is called Orthokin, which is a normal product of monocytes and is prepared within autologous conditioned serum (ACS) from the patient’s own blood cells. It is capable of blocking the effects of IL-1, including the induction of matrix metalloproteinases, prostaglandin E2 synthesis, and expression of other cytokines.


The aim of the study was to clinically evaluate the effect of intra-articular injection of low-dose ACS enriched with Orthokin on primary knee osteoarthritis to assess its validity in treatment.

Patients and methods

This study included 30 knees with primary osteoarthritis. Baseline clinical evaluation using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score was performed. Then ACS enriched with Orthokin (IL-1 receptor antagonist) was prepared. The knee joint was injected with 1 ml ACS weekly for 3 successive weeks. Patients were assessed using WOMAC questionnaire (1 week after each injection for 3 weeks and monthly after the last injection for 3 months).


On comparing WOMAC score with baseline data, there was a highly significant improvement in all scores, where P was less than 0.01 during all assessment periods and improvement persisted until the end of follow-up after 3 months in comparison with baseline data.


The synthesis and introduction of interleukin-1 receptor antagonists derived from own blood cells established a promising strategy in the treatment of osteoarthritis.


  1. Jain A, Singh SK, Singh Y, Singh S. Development of lipid nanoparticles of diacerein, an antiosteoarthritic drug for enhancement in bioavailability and reduction in its side effects. J Biomed Nanotechnol 2013; 9:891–900.

    Article  CAS  Google Scholar 

  2. Malemud CJ. Anticytokine therapy for osteoarthritis: evidence to date. Drugs Aging 2010; 27:95–115.

    Article  CAS  Google Scholar 

  3. Ragle RL, Sawitzke AD. Nutraceuticals in the management of osteoarthritis: a critical review. Drugs Aging 2012; 29:717–731.

    Article  CAS  Google Scholar 

  4. Davies PS, Graham SM, MacFarlane RJ, Leonidou A, Mantalaris A, Tsiridis E. Disease-modifying osteoarthritis drugs: in vitro and in vivo data on the development of DMOADs under investigation. Expert Opin Investig Drugs 2013; 22:423–441.

    Article  CAS  Google Scholar 

  5. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986; 29:1039–1049.

    PubMed  CAS  Google Scholar 

  6. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957; 16:494–502.

    Article  CAS  Google Scholar 

  7. Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res 2003; 52:404–407.

    Article  CAS  Google Scholar 

  8. JG Rogers, JJ Irrgang. Western Ontario and Macmaster Universities Index. Measures of adult lower extremity function. Arthritis Rheum 2003; 49:S67–S84.

    Google Scholar 

  9. Wehling P, Moser C, Frisbie D, McIlwraith C, Kawcak CE, Krauspe R, et al. Reinecke: Knee Osteoarthritis. Randomized Controlled Trials. ACS in Clinical Human Studies. Autologous conditioned serum in the treatment of orthopedic diseases. The Orthokine Therapy. Biodrugs 2007; 21:328–329.

    Google Scholar 

  10. Baltzer AWA, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage 2009; 17:152–160.

    Article  CAS  Google Scholar 

  11. Yang KG, Raijmakers NJ, VanArkel ER, Caron JJ, Rijk PC, Willems WJ, et al. Autologus interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial 1. Osteoarthritis Cartilage 2008; 16:498–505.

    Article  Google Scholar 

  12. Baltzer AWA, Ostapczuk MS, Stosch D, Seidel F, Granrath M. A new treatment for hip osteoarthritis: clinical evidence for the efficacy of autologous conditioned serum. Orthop Rev (Pavia) 2013; 5:59–64.

    Article  Google Scholar 

  13. Chevalier X, Giraudeau B, Conrozier T, Marliere J, Kiefer P, Goupille P. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis a multicenter study. J Rheumatol 2005; 32:1317–1323.

    PubMed  CAS  Google Scholar 

  14. Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, Conrozier T, et al. Intra-articular injection of anakinra in osteoarthritis of the knee. A multicenter randomized double blind placebo controlled study. Arthritis Rheum 2009; 61:344–352.

    PubMed  CAS  Google Scholar 

  15. Suneela D, Dipmala P. Synthesis and pharmacokinetic profile of rheinboswellic acid conjugate. Bioorg Med Chem Lett 2012; 22:7582–7587.

    Article  CAS  Google Scholar 

  16. Fidelix TS, Macedo CR, Maxwell LJ, Fernandes Moça Trevisani V. Diacerein for osteoarthritis. Cochrane Database Syst Rev 2014; 2:CD005117.

    Google Scholar 

  17. Brahmachari B, CS Ghosh. Efficacy and safety of diacerein in early knee osteoarthritis. A randomized placebo-controlled trial. Clin Rheumatol 2009; 28:1193–1198.

    PubMed  Google Scholar 

  18. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014; 22:363–388.

    Article  CAS  Google Scholar 

  19. Namazi H, Majd Z. Botulinum toxin as a novel addition to anti arthritis armamentarium. Am J Immunol 2005; 1:94–95.

    Article  CAS  Google Scholar 

  20. Chou CL, Lee SH, Lu CY, Tsai KL, Ho CY, Li HC. Theraputic effects of ıntra-articular botulinum neurotoxin in advanced knee osteoarthritis. J Chin Med Assoc 2010; 73:573–580.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Mahmoud M. Fathalla MD.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Motaal, F.K.AE., Elganzoury, A.M., Fathalla, M.M. et al. Low-dose intra-articular autologous conditioned serum in treatment of primary knee osteoarthritis. Egypt Rheumatol Rehabil 41, 98–102 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • autologous conditioned serum
  • interleukin-1 receptor antagonist
  • osteoarthritis
  • WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)