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 cytoki nes and type I collagen, fixed synovium T cell clones were cocultured on sy noviocytes and levels of IL-6, LIF and PICP, a marker of type I collagen sy nthesis 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 incr eased with Th-2 clones. IL-17-producing T cells, all Th-1, were among the h ighest inducers of cytokine and inhibitors of collagen synthesis. Preincuba tion of clones in Th-2 conditions (IL-12 plus anti-IL-4) increased IL-6 pro duction, whereas Th-2 conditions (IL-4 plus anti-IL-12) strongly inhibited IL-6 production and restored repair activity. As rheumatoid synovium is inf iltrated by Th-1 cells, local cell interactions result in a pro-inflammator y pattern with defective repair, which can be reversed at least in part, by a Th-2 pattern. (C) 2001 Academic Press.