GOLDIC’s Inflammatory and Regenerative Action

Actin Embracing Gelsolin

The use of autologous-conditioned serum in the treatment of several degenerative diseases is of increasing interest in the field of human and equine medicine. Several clinical studies show beneficial results [5]. IL-1 blocking activities seem to be the most important factor in this treatment strategy [6,7]. In the IRAP/ORTHOKIN-procedure, this could be achieved by using glass beads exposed to chromium sulfate as a method to stimulate peripheral WBCs [2]. In our own in vitro studies, gold particles were used instead of glass beads to stimulate a biological response of blood cells [4].

Gold is a very well know element in the treatment of several rheumatic diseases. Analyzing the actions of gold in the different phases of an immune reaction suggests that gold plays an important role already in the initiation, namely, the uptake and presentation of foreign antigens. Thus, gold is taken up by the macrophages and stored in the lysosomes, which are called aureosomes, where gold inhibits antigen processing. Moreover, it has been shown that gold suppresses NF-kappa B binding activity, as well as, the activation of the I-kappa B-kinase. This mechanism results in a subsequently reduced production of proinflammatory cytokines, most notably TNF-alpha, interleukin-1 and interleukin-6. On the subsequent T-cell level, gold has been shown to induce an up-regulation of IL-4 mRNA, resulting in a shift of the T-cell population to the Th2 phenotype. Moreover, the activation of T-cells is inhibited [8].

Arthrogen’s new approach using gold particles to interact with blood cells in an extra-corporal setup is utilized in GOLDIC (gold-induced cytokines). After a 24 hour incubation period and subsequent centrifugation, the resulting serum is injected into the patient’s injury. A total of four injections are given over a period of approximately 2-3 weeks. The therapy is well tolerated with no side-effects noted.

The analysis of blood samples with human blood showed that the GOLDIC technology triggers increased production of certain cytokines and important proteins like gelsolin [4]. Gelsolin is a highly conserved, multifunctional actin-binding protein with an extracellular isoform, plasma gelsolin, for which there is not yet a clearly defined function. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin-scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, liver injury, rheumatoid arthritis, cancer, apoptosis, infection and inflammation, cardiac injury, pulmonary diseases, and aging [9]. This protein also plays a key role in the differentiation of stem cells to cartilage cells [10]. The activation of stem cells via a gelsolin-mediated regeneration process can be seen as a new approach to stimulate the body’s own repair processes.

(Please see entire study: First Results on the Outcome of Gold-induced, Autologous-conditioned Serum (GOLDIC) located in the reference tab).

Gold-IC-Aqua-Spec


Gold-IC-Elisa-Presence


Gold-IC-Elisa-Gelsolin

References

  1. Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW (2007) Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res 68: 290-296.
  2. Meijer H, Reinecke J, Becker C, Tholen G, Wehling P (2003) The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res 52: 404-407.
  3. Hraha TH, Doremus KM, McIlwraith CW, Frisbie DD (2011) Autologous conditioned serum: the comparative cytokine profiles of two commercial methods (IRAP and IRAP II) using equine blood. Equine Vet J 43: 516-521.
  4. Schneider U (2011) International Patent Application No. PCT/DE2011/001322.
  5. Wehling P, Moser C, Frisbie D, McIlwraith CW, Kawcak CE, et al. (2007) Autologous conditioned serum in the treatment of orthopedic diseases: the orthokine therapy. BioDrugs 21: 323-332.
  6. Bresnihan B, Alvaro-Gracia JM, Cobby M, Doherty M, Domljan Z, et al. (1998) Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 41: 2196-2204.
  7. Campion GV, Lebsack ME, Lookabaugh J, Gordon G, Catalano M (1996) Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. The IL-1Ra Arthritis Study Group. Arthritis Rheum 39: 1092-1101.
  8. Burmester GR (2001) [Molecular mechanisms of action of gold in treatment of rheumatoid arthritis–an update]. Z Rheumatol 60: 167-173.
  9. Li GH, Arora PD, Chen Y, McCulloch CA, Liu P (2012) Multifunctional roles of gelsolin in health and diseases. Med Res Rev 32: 999-1025.
  10. Djouad F, Delorme B, Maurice M, Bony C, Apparailly F, et al. (2007) Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes. Arthritis Res Ther 9: R33.
  11. McIlwraith CW, Frisbie DD, Kawcak CE (2012) The horse as a model of naturally occurring osteoarthritis. Bone Joint Res 1: 297-309.

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