Enhanced expression of high-affinity interleukin-2 receptors in scleroderma: possible role for IL-6.
Scleroderma (systemic sclerosis) is characterized by tissue fibrosis, a distinctive vascular and microvascular disorder, and a perivascular mononuclear cell infiltration of involved organs. The pathogenesis of scleroderma is not known; however, there is evidence for a cell-mediated immune mechanism in the disease. Enhanced IL-2 production has been documented both in vivo and in vitro. In this study, the effect of IL-2 on lymphocyte proliferation in vitro was examined. An enhanced proliferative response to IL-2 was seen in scleroderma lymphocytes over that in matched control lymphocytes. Since high-affinity IL-2 receptors (HIL-2-R) mediate the growth-promoting activity of IL-2, we examined HIL-2-R expression on lymphocytes from 13 scleroderma and 11 matched control subjects by a radioiodinated IL-2 binding assay. Significantly higher numbers of HIL-2-R were noted in scleroderma cells (3054 +/- 618 in scleroderma vs 1721 +/- 181 in control cells, mean +/- SD; P less than 0.001). The addition of IL-6 to control cell cultures 24 hr prior to binding determination led to changes in IL-2 binding that were identical to scleroderma cell binding characteristics, while the addition of neutralizing IL-6 antibody to scleroderma cells led to a reduction in HIL-2-R expression. Other cytokines (IL-1, IL-3, IL-4, IL-5, TNF, LT, IFN-gamma, and TGF-beta) had no effect on IL-2 binding, suggesting that IL-6 may mediate the enhanced expression of HIL-2-R. This conclusion was further supported by the finding that scleroderma lymphocytes released in vitro 10- to 20-fold higher concentrations of IL-6 than control cells. The data demonstrate an amplification of IL-2 binding in scleroderma and suggest IL-6 as the mediator of this phenomenon.
Kahaleh
M B
MB
Department of Medicine, Medical College of Ohio, Toledo 43699-0008.
Yin
T G
TG
D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000502:physiology*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D012595:Scleroderma, Systemic / Q000209:etiology / Q000276:immunology*
D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2