The dual role of the SNS depends on involved compartments, on timing of effector mechanisms during the inflammatory process, on availability of adrenoceptors on target cells, and on an intricate shift from b- to a-adrenergic signaling in the progressing course of the disease. A further critical point for the dual role of the SNS in inflammation is the underlying change of immune effector mechanisms during the process of disease progression and also the behaviour of sympathetic nerve fibres (SNF). In chronic inflammatory diseases, we observe a loss of SNF due to the expression of nerve repellent factors. Interestingly, SNF are "replaced" by sympathoadrenal chromaffin-like cells (SAC), which express the entire apparatus of catecholamine synthesizing enzymes. Density of SAC is markedly higher in patients with rheumatoid arthritis as compared to osteoarthritis. Catecholamine secretion of these SAC seems to be a proinflammatory signal due the chemotactic effects elicited. Furthermore, inhibition of catecholamine secretion from SAC leads to a marked decrease of TNF secretion. These events are accompanied by a relative lack of adrenal anti-inflammatory glucocorticoids in relation to inflammation. In quintessence, in very early stages of inflammatory joint disease, the SNS plays a predominant pro- inflammatory role whereas in late stages of the disease the SNS most probably exerts anti-inflammatory effects but SAC play a proinflammatory role.