In that previous studies have suggested that certain antibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies, are present several years before rheumatoid arthritis develops, and that other research has suggested that certain inflammatory factors are present before disease onset and can be detected at higher levels in early disease than in late disease, Heidi Kokkonen, from Umea University Hospital (Sweden), and colleagues analyzed plasma samples from a population-based registry in northern Sweden, assessing the levels of thirty cytokines, cytokine receptors, and chemokines from a population-based registry in northern Sweden. The team found that concentrations of two-thirds of proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and eotaxin were significantly increased in subjects who later developed rheumatoid arthritis, Further, the team found significant correlations between the presence of anti-cyclic citrullinated peptide (CCP) antibodies and cytokine positivity, noting associations that were more pronounced for Th2-related cytokines as compared to Th1 cytokines or for cytokines involved in general immune upregulation.  The researchers conclude that: “Individuals in whom [rheumatoid arthritis] later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.”