Monday, October 10, 2011

Review of the Implications of MOM hips to cancer addressing the creation of abnormal chromosomes (genotoxic effects-in the last post-), Immune Mediated responses (below) and oxidation of Cr 3 to 6 and visa versa-next post-. (2 of 3)

Immune mediated responses

Cell-mediated immunity defends against intracellular pathogens like metals.

Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells (NK),  and antigen-specific cytotoxic T-lymphocytes.

Cellular immunity protects the body by:

  1. activating antigen-specific cytotoxic T-lymphocytes that are able to induce apoptosis in body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;
  2. activating macrophages and natural killer cells, enabling them to destroy pathogens; and
  3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.

The real question here is what happens when you have continued unchecked inflammation? 

It has been shown in the literature that chromium 3 (the non toxic trivalent form) can produce carcinogenic mechanisms by stimulating the immune response through inflammation. If the inflammation goes unchecked, then this can contribute to the development of the cancer. The literature is all environmental evidence and not evidence that shows a link between the hip and cancer. The one fact is that inflammation is known as a progressive factor in causing cancers environmentally. [McCabe et al]

The best paper on this  subject I found was Metal-on-metal hip resurfacing athroplasty/ A review of periprosthetic biological reactions.  A review of this post can be found in the following blog post:
Review of the Cell biology surrounding metal on metal hips (4 of x in a series) from the University of Oxford:

  • Chromium and cobalt (contained in the metal on metal hips) have an effect on cells that is different to that of polyethylene and most other biomaterial.

  •   The metal particles are often phagocytosed (engulfed and then digested) by macrophages (white cells that digest debris-like metal.)

  •  Once phagocytosed, Chromium and cobalt particles can be toxic and rapidly kill the cells. This is likely because they corrode quickly within the cells due to the acidic environment in the cell and then release ions in high concentrations within the cells leading to toxicity.

  •   The cells then lyse (breaking down of the cell), releasing the particles and cell contents to cause further damage.

  • Release of metal particles and metal ions can have further adverse effects:  they can be transported to areas other than the joint cavities and initiate further osteolysis away from the affected joint area
Co And Cr ions are toxic for osteblasts ( cells that make bone) and Co ions induce the death of osteoclasts (removes bone tissue.)

[ added by connie:  Metal ion concentrations not directly cytotoxic to lymphocytes may affect events at a molecular level, thereby impeding lymphocyte proliferation. Hence, this may contribute to altered immune system function in patients with Co-Cr implants. All of this is Important because lymphocytes fight infection. Prolonged inflammation from infection can result in long term issues which potentially could be carcinogenic.]

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