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IL-4 secreted by activated T cells has anti-angiogenic effects by inhibiting VEGF production in RA FLS, which helps relieve RA ( + T cells population ( via activation of protein kinase C (PKC) / II and ERK-1/2, with concomitant down-regulation of the NF-B/p65 pathway ( via activating Smad-2/3 in RA ( ( Figure 1 )
Michelazzi MB, Greta & Talamonti, Z
However, the regulatory framework for drug development relies heavily on animal toxicology precisely because it does provide meaningful safety signals
It provides enough doses for meaningful protocol duration without the waste risk of larger vials at lower doses
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