The Lyme Disease Network
Medical / Scientific Abstract
|Title:||Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.|
|Authors:||Finnegan A, Mikecz K, Tao P, Glant TT|
|Source:||J Immunol 1999 Nov 15;163(10):5383-90|
|Organization:||Department of Medicine, Section of Rheumatology, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. email@example.com|
In animal models of arthritis induced with Ags or infectious agents, disease severity correlates with a dominant Th1-type response characterized by a higher ratio of IFN-gamma to IL-4. Analysis of BALB/c mice revealed a genetic predisposition toward developing CD4+ Th2-type responses. The bias toward an IL-4-dominant response in BALB/c mice protects mice from severe Lyme-induced arthritis and spontaneous autoimmune disease. Since BALB/c mice immunized with proteoglycan develop severe arthritis, we were interested in testing whether arthritis is associated with a Th2-type response and thus is different from other arthritic models. BALB/c mice immunized with proteoglycan generated a higher ratio of IFN-gamma to IL-4 that peaks at the onset of arthritis. We investigated whether when Th1 cells were dominant, disease outcome could be modified with pharmacological amounts of Th2 cytokines. Treatment with IL-4 prevented disease and induced a switch from a Th1-type to a Th2-type response. Proinflammatory cytokine mRNA transcripts were reduced in joints of cytokine-treated mice. Th2 cytokine therapy at the time of maximum joint inflammation also suppressed symptoms of disease. Despite the predisposition of BALB/c mice to a Th2-type response, proteoglycan-induced arthritis is a Th1-type disease. The effectiveness of IL-4 treatment was particularly striking because in other models of arthritis, treatment in a similar manner with IL-4 was not sufficient to inhibit arthritis. The effective control of arthritis and the switch from a Th1 to Th2 response suggest that levels of endogenous IL-4 in BALB/c mice may increase their responsiveness to Th2 cytokine therapy.
Acute Disease, Animal, Anti-Inflammatory Agents, Non-Steroidal, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Arthritis, Adjuvant, ETIOLOGY, IMMUNOLOGY, PATHOLOGY, PREVENTION &, CONTROL, Cytokines, ADMINISTRATION & DOSAGE, BIOSYNTHESIS, PHYSIOLOGY, THERAPEUTIC USE, Female, Human, Immunization, Injections, Intraperitoneal, Interferon Type II, ANTAGONISTS & INHIB, BIOSYNTHESIS, Interleukin-4, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Interleukin-6, ANTAGONISTS & INHIB, BIOSYNTHESIS, GENETICS, Kinetics, Lymphotoxin, ANTAGONISTS & INHIB, BIOSYNTHESIS, GENETICS, Mice, Mice, Inbred BALB C, Proteoglycans, ADMINISTRATION & DOSAGE, IMMUNOLOGY, RNA, Messenger, ANTAGONISTS & INHIB, BIOSYNTHESIS, Support, U.S. Gov't, P.H.S., Th1 Cells, IMMUNOLOGY, METABOLISM, SECRETION, Th2 Cells, IMMUNOLOGY, METABOLISM, SECRETION, Tumor Necrosis Factor, ANTAGONISTS & INHIB, BIOSYNTHESIS, GENETICS
Unique ID: 20021834
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