1. Clinical Aspects of Immune Neuroendocrine Mechanisms in Rheumatic Diseases 
Johannes W.J. Bijlsma, MD, PhD, Maurizio Cutolo, MD, Rainer H. Straub, MD, Alfonse T. Masi, MD, DrPH 
Rheumatic Disease Clinics 
Volume 31, Issue 1, Pages xiii-xvi (February 2005)
DOI: /j.rdc
Copyright © 2005 Elsevier Inc. Terms and Conditions

2. Fig. 1
Integrated view of influencing factors on chronic inflammatory rheumatic diseases. The basis of rheumatic disease is a genetic background in which several important polymorphisms have been suggested to play a role (gray area in the online version). These genetic polymorphisms are the precursors for rheumatic diseases. During early life, an asymptomatic phase of the disease exists during which serologically detectable autoimmune phenomena may be detected (yellow area in the online version); autoantibodies can be observed years before disease outbreak. Respective environmental triggers may play an initiating role in this early phase. Adaptive immune responses also play a dominant role (dendritic cells, T cells, B cells). In addition, nervous and endocrine factors can intensely modulate leukocyte migration and distribution. In the symptomatic overt phase of the disease (red area in the online version), the roles of the initial players—the T cell, B cell, and dendritic cell—simultaneously decrease while other cell types in the inflamed area step in. Stress axes mediators may stimulate the immune response in stress phase S1, but the same mediators can inhibit immune response in stress phase S2. These differential effects are due to the different components involved. Furthermore, in the asymptomatic phase of the disease (yellow area in the online version), neuroendocrine axes may be activated, whereas in the symptomatic phase these axes are markedly altered, possibly as a result of inherited deficits in responding to inflammation. ACE; angiotensin converting enzyme; CRH, corticotropin releasing hormone; FCγRIIIA; Fc-gamma receptor IIA; GRβ; glucocorticoid receptor beta; IL-10, interleukin 10; MHC, major histocompatibility complex; MMP-3; matrix metalloproteinase 3; PADI; peptidylarginine deiminase 4 (initiates cyclic citrullination); SLC22A4; organic cation transporter; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor.
Rheumatic Disease Clinics  , xiii-xviDOI: ( /j.rdc )
Copyright © 2005 Elsevier Inc. Terms and Conditions