Effect of IFN-gamma, IL-4 on proliferation and synthesis of hyaluronic acid and collagen in cultured human retroorbital fibroblasts in vitro.
OBJECTIVE
To investigate the cellular immune mechanism of thyroid associated ophthalmopathy (TAO) and provide a basis for treating TAO with cytokine or anti-cytokine agents, we determined whether interferon (IFN)-gamma and interleukin (IL)-4, representative cytokines of Th1 and Th2 cells, may have some effect on the development and progression of TAO.


METHODS
Retroorbital fibroblasts (RF) proliferation and the synthesis of hyaluronic acid (HA) and type IV collagen were measured with liquid scintillation and radioimmunoassay.


RESULTS
IFN-gamma stimulated RF proliferation and HA synthesis and had a significant inhibitory effect on type IV collagen synthesis. IL-4 stimulated proliferation and type IV collagen synthesis in RF and had inhibitory effect on HA synthesis. When IFN-gamma (100 U/ml) and IL-4 (1 microgram/L) were incubated together with RF, they antagonized their respective stimulatory or inhibitory effect on the proliferation and synthesis of HA and type IV collagen. Thyrotropin (TSH) stimulated RF proliferation and type IV collagen synthesis in a dose-dependent manner, while only at high dose (100 U/L and 200 U/L), stimulated RF to synthesize HA.


CONCLUSIONS
IFN-gamma, a representative cytokine of Th1 cells, is responsible for the inflammatory process of TAO; whereas IL-4, a representative cytokine of Th2 cells, has some effect on the repair process. IL-4 could antagonize the inflammatory effect of IFN-gamma on RF. TSH may have aggravating effect on the pathogenesis of TAO.
Wang
L
L
Department of Endocrinology, Second Hospital of China Medical University, Shenyang 110003, China. xdliu@mail.sy.ln.cn
Teng
W
W
Shan
Z
Z
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006111:Graves Disease / Q000209:etiology* / Q000276:immunology; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D013972:Thyrotropin / Q000494:pharmacology
D015847:Interleukin-4; D007371:Interferon-gamma; D013972:Thyrotropin; D006820:Hyaluronic Acid; D003094:Collagen