Inhibition of S1P led to decreased serum levels of pro-inflammatory TNF-α, IL-1β, and IL-6 and reduced arthritis activity in previous in vivo experiments (Lai et al., 2008; Alvarez et al., 2010), allowing the assumption that S1P is a key regulator of TNF-α stimulated IL-1β and IL-6 release in RA. This evidence concerns the gene IL6 and rheumatoid arthritis.