A method to induce Interleukin-1 Receptor Antagonist Protein from autologous whole blood

Cytokine. 2016 May:81:137-41. doi: 10.1016/j.cyto.2016.03.008. Epub 2016 Mar 16.


Objective: Current orthopedic therapies, aimed solely at symptomatic control, are unable to restore the cytokine imbalance that produces the hallmark clinical profile of osteoarthritis. While a myriad of chemical factors in the cytokine network stimulate local joint inflammation and pain, Interleukin 1 (IL-1) is widely recognized as a key offender and a potential therapeutic target. The purpose of this article is to describe a novel, on-site, point of service process (Arthrokinex™) to induce Interleukin 1 Receptor Antagonist Protein (IL-1-Ra or IRAP) from whole blood aimed at inhibiting the destructive intra-articular effects of IL-1.

Methods: 53 patient charts were included in this retrospective chart review study. Venous blood from the selected participants had been harvested and centrifuged to isolate Platelet Rich Plasma and Platelet Poor Plasma. These layers were extracted and incubated for 30 min in a specialized syringe containing medical grade concentrator beads. After centrifuge filtration, the supernatant containing IL-1-Ra was extracted. Anti-inflammatory (IL-1-Ra, IL-10) and pro-inflammatory (TNF α, IL-1 β) cytokines of baseline whole blood were compared to the conditioned serum following quantification using ELISA.

Results: On average, a 32-fold increase (baseline, 550 pg/mL; post conditioning 17,537 pg/mL) in IL-1-Ra concentration was observed after the brief interaction of blood with the concentrator bead surface. IL-1-Ra, if present in concentrations that are 10-100 times higher than IL-1β, will block the interaction of IL-1β with cell surface receptors. At these increased concentrations, Arthrokinex™ induced IL-1-Ra joint injections produce an IL-1-Ra to IL-1β ratio of 999:1. Post conditioning levels of IL-1β and TNF α were not clinically significant.

Conclusion: The Arthrokinex™ blood conditioning process has the ability to rapidly induce IL-1-Ra without increasing the pro-inflammatory cytokine profile.

Keywords: Arthrokinex™; IL-1-Ra; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Chemical Analysis / methods*
  • Blood Preservation / methods
  • Centrifugation / methods
  • Cryopreservation / methods
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Filtration / methods
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / blood*
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Male
  • Middle Aged
  • Osteoarthritis / blood*
  • Point-of-Care Systems
  • Reproducibility of Results
  • Retrospective Studies
  • Tumor Necrosis Factor-alpha / blood


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10