Interleukin-7 in rheumatoid arthritis.
Recent data from several groups demonstrate high levels of IL-7 in the joints of RA patients, but much lower levels in OA. In contrast, circulating levels of IL-7 in RA remain a point of debate. IL-7 has many roles in T cell, dendritic cell and bone biology in humans. Reduced levels of circulating IL-7 probably underlie a number of the dysfunctions associated with circulating T cells in RA and may provide a mechanism for some of the unexplained systemic manifestations of the disease. However, IL-7 in the joint may have a more sinister role, contributing to a vicious cycle perpetuating inflammation. Typically, IL-1beta and TNF-alpha increase the stromal production of IL-7 and in turn, IL-7 up-regulates the production of TNF-alpha by macrophages. Most importantly, IL-7 induces the production of osteoclastogenic cytokines by T cells, leading to the maturation of osteoclasts and therefore bone destruction. By linking the stroma with innate and adaptive immunity in RA, IL-7 may be directing the cellular network, leading to chronic inflammation and joint destruction. Blocking IL-7 may well therefore be of therapeutic value.
Churchman
S M
SM
The University of Leeds, Leeds Institute of Molecular Medicine, Section of Musculoskeletal Disease, St James's University Hospital, Leeds, LS9 7TF, UK.
Ponchel
F
F
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D001842:Bone and Bones / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
D018501:Antirheumatic Agents; D015851:Interleukin-7