OK pofaced: having looked at both papers I interpret the following:
- These are studies of a specific animal model of rheumatoid arthritis, with the animals being genetically inbred to be prone to that disease. Injection of squalene intradermally appears to provoke an arthritis along the lines of their genetic susceptibility.
- The first paper shows that intradermal injection of squalene can cause a flare of arthritis in these susceptible rats, peaking at 21 days but subsiding thereafter. It is suggested that the immune response is CD4-mediated rather than via CD8 cells.
- The second paper attempts to track injected squalene to various body compartments using a radioactive labelling technique. The results suggest the injection of squalene has a direct effect on the immune system cells in the lymph nodes - rather than an accumulation in the joints themselves - and that the arthritic effects of activated immunity can be transferred to squalene-naive rats via the immune cells.
I guess you might be wondering whether this has a link with squalene adjuvant in humans...
First of all, these studies are in rats, and rats aren't always a great model for what happens in humans. For immunity and infectious diseases, mice are the more consistent model.
Secondly, if you look at how much squalene these rats are getting (200-300 uL per 0.5kg rat), it is huge: multiplied up to a 70kg human dose that's about 35mL per person. Since squalene is lighter than water and has a specific gravity of ~0.88, that makes about 28g per equivalent inoculation. Now, the MF59-based seasonal flu vaccine has 10 micrograms of squalene per dose: approx three million times less. That's very significant on a biological scale and probably why squalene adjuvants have not been shown to cause or aggravate chronic immunological conditions in humans.
Animal modes are a valuable first step in evaluating drugs and vaccines, but the best demonstration remains with the human trials. If ten years worth of MF59-based seasonal flu vaccines in Europe isn't enough of a demonstration, then the GSK trials of the AS03-based H5N1 vaccine specifically looked for neurological and chronic immunological developments for 6 months post-vaccination in about 10,000 people, versus non-adjuvanted seasonal vaccination in about 12,000 people. The autoimmune syndromes looked for were thyroiditis or Graves disease, polyarteritis nodosa, Sjogren?s syndrome, ocular myasthenia, uveitis, PMR / temporal arteritis... and there were 6 in the AS03 group and 5 in the non-AS03 group.
So basically the rats studies are interesting in their own right as studies of what might cause rheumatoid arthritis in rats, but for the above reasons I would discount their relevance to the human world; especially when there is a large amount of direct human comparative data available.