Cytokines are proteins secreted by cells that serve as intercellular mediators (see Table 57-1). An imbalance of proinflammatory and anti-inflammatory cytokines in the synovium leads to inflammation and joint destruction. The proinflammatory cytokines interleukin 1 (IL-1), tumor necrosis factor-a (TNF-a), IL-6, and IL-17 are found in high concentration in synovial fluid. These proinflammatory cytokines cause the activation of other cytokines and adhesion molecules responsible for the recruitment of lymphocytes to the site of inflammation. Anti-inflammatory cytokines and mediators (IL-4, IL-10, and IL-1 receptor antagonist) are present in the synovium, although concentrations are not high enough to overcome the effects of the proinflam-matory cytokines.4,9

Table 57-1 Cytokines Involved in the Pathogenesis of RA






MacropKvjei, moncr/tief. R lymphocyte?,

Indices IL-l.U-6. Il-H, siimuljie* fibroblasts to

T lympixxytes, Fibroblasts

release adhesion molecules


uaaophic)«, moncïifiici,(fldi3twlii c^fc.

ttiiiiul.Wdihtrtïl.Wt JrUifhiïi(1i[X>T« to ri'liMU^ rtVilrix

fl tyiT y!«, activated T lymphocytes



T lymp'iCi yies irtOrKuy!«! «rut nophù^ei, synOfijl

*s.tivjHr> T lymplux y1e\. 1ndu<tl*CUte-ptlHeiHp0ftS4


stimulate! oiiïAih and differentiation of hematopoleiic piecursor cells, stimulates synovial fibtoblasts


T lympltKX yTÎ^ in ^yflflviym

SylVrilbIt tff«l will' H I -irhh TNJ li'.ul to irtf ii'.im^J pioducllonof proinflammatory cytokines


CP4-+- iype 1 help« T lymphocyte*

irihihu af livattem of type 1 helper T lymphocytes ClMltdSM piOduCtkiitOf IL-1. TNF


Monocytes. maciophsçt«. 6 lymphocyte?.

Inhibits pioduciionof IL-1. TNF-a and prolifération of T

T lymphocytes


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Anxiety and Depression 101

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