Current model of sympathetic nervous system influence in arthritis. In early arthritis (left panel), the sympathetic nervous system (SNS) supports inflammation in the joint through a proinflammatory influence on adaptive immune cells; for example, increased specific antibody production by B cells and increased proinflammatory activity of T cells. The SNS also inhibits innate immune cells via stimulation of β2 adrenoceptors (β2ARs), although the net outcome of SNS influence in the early phase is proinflammatory. Then, during the transition phase, we hypothesize that the influence of the SNS changes from pro- to anti-inflammatory. In the later stages, central regulation of the inflammatory process is less important, since sympathetic nerve fibers are repelled from the inflamed area and secondary lymphoid organs. However, local sympathetic influence becomes increasingly important, indicated by the appearance of catecholamine-producing, tyrosine hydroxylase-positive (TH+) cells, which have a dominant anti-inflammatory effect. Possible mechanisms of action are paracrine and autocrine in manner; for example, inhibiting proinflammatory interleukin (IL)-7 receptor-positive B cells, increasing the activity of IL-10-producing anti-inflammatory B cells, or inhibiting innate immune cells via β2AR-mediated effects. AR, adrenoceptor; cAMP, cyclic adenosine monophosphate; CD, cluster of differentiation; FoxP3, forkhead box P3; IFN, interferon; MHC, major histocompatibility complex; pSTAT5, phosphorylated-signal transducer and activator of transcription 5; TCR, T-cell receptor; Th1, T helper 1 cell.