Modulating the Th1/Th2 balance in inflammatory arthritis.
The balance between Th1 and Th2 cells regulates the choice between inflammatory and antibody-mediated immune responses. To an increasing extent this balance is thought to involve the participation of antigen-presenting cells, rather than the entirely autonomous activity of T cells and their cytokines. Here we survey current opinion concerning the working of this balance, and its condition in rheumatoid arthritis and the other inflammatory arthritides. The contrast between Lyme arthritis and reactive arthritis is particularly illuminating, since one is triggered by extracellular and the other by intracellular infection. We describe current approaches to the modulation of this balance. Guided by the principles that genetic polymorphism is likely to identify relevant genes, that any cytokine gene picked up by a virus must matter and that natural immunosuppressive activity at mucosal surfaces should be worth exploiting, we identify as particularly worthy of attention: (i) IL-10, (ii) inhibitors of IL-12 production, (iii) inhibitors of CD40 ligand expression and (iv) oral and nasal tolerance. Other protective T cell subsets are touched on, and the impact of oligonucleotide arrays mentioned.
Müller
B
B
Deutsches Rheuma Forschungs Zentrum, Berlin, Germany.
Gimsa
U
U
Mitchison
N A
NA
Radbruch
A
A
Sieper
J
J
Yin
Z
Z
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000517:prevention & control; D001170:Arthritis, Infectious / Q000276:immunology; D016918:Arthritis, Reactive / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D015415:Biomarkers; D019013:CD40 Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D008193:Lyme Disease / Q000276:immunology; D051379:Mice; D009061:Mouth Mucosa / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology; D011247:Pregnancy; D011376:Progesterone-Binding Globulin / Q000276:immunology; D012738:Sex Hormone-Binding Globulin / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D015415:Biomarkers; D019013:CD40 Antigens; D011376:Progesterone-Binding Globulin; D012738:Sex Hormone-Binding Globulin; D016753:Interleukin-10; D018664:Interleukin-12