Potential contribution of IL-17-producing Th(1)cells to defective repair activity in joint inflammation: partial correction with Th(2)-promoting conditions.
To assess the contribution of cell interactions to the production of cytokines and type I collagen, fixed synovium T cell clones were cocultured on synoviocytes and levels of IL-6, LIF and PICP, a marker of type I collagen synthesis measured. Levels of IL-6 and LIF were higher with Th(1)than with Th(0)and Th(2)clones. Levels of PICP were decreased with Th(1)clones and increased with Th(2)clones. IL-17-producing T cells, all Th(1), were among the highest inducers of cytokine and inhibitors of collagen synthesis. Preincubation of clones in Th(1)conditions (IL-12 plus anti-IL-4) increased IL-6 production, whereas Th(2)conditions (IL-4 plus anti-IL-12) strongly inhibited IL-6 production and restored repair activity. As rheumatoid synovium is infiltrated by Th(1)cells, local cell interactions result in a pro-inflammatory pattern with defective repair, which can be reversed at least in part, by a Th(2)pattern.
Chabaud
M
M
Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, 69437 Lyon Cedex 03, France.
Aarvak
T
T
Garnero
P
P
Natvig
J B
JB
Miossec
P
P
D001172:Arthritis, Rheumatoid / Q000378:metabolism; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis; D003470:Culture Media / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006131:Growth Inhibitors / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D007596:Joints / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis; D013582:Synovial Fluid / Q000166:cytology*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D003470:Culture Media; D006131:Growth Inhibitors; D020381:Interleukin-17; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D018664:Interleukin-12; D015847:Interleukin-4; D003094:Collagen