Mechanisms of pathogenesis in scleroderma. I. Overproduction of interleukin 6 by fibroblasts cultured from affected skin sites of patients with scleroderma.
Fibroblasts were cultured from affected skin sites of patients with progressive systemic sclerosis (PSS), from unaffected skin sites of the same patients, and from a healthy donor. The concentration of interleukin 6 (IL-6) in culture medium conditioned by the growth of early passage cells was determined by radioimmunoassay and by quantitative bioassay. Results demonstrated that fibroblasts from affected PSS skin produce from 6 to 30-fold higher levels of biologically active IL-6 compared to unaffected and control cells. In contrast, serum IL-6 concentrations in 6 of 8 patients examined were not significantly different from healthy donors. Serum IL-6 levels were elevated 2 to 3-fold in 2 of 8 patients examined. Thus, the overproduction of IL-6 by affected scleroderma fibroblasts does not necessarily correlate with a systemic increase in IL-6, but may increase its concentration locally. In view of its biological activities, including stimulation of antibody production and T cell activation, the overproduction of IL-6 by PSS fibroblasts in the lesions may play a significant role in the pathogenesis of PSS and may profoundly influence the course of the disease.
Feghali
C A
CA
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112.
Bost
K L
KL
Boulware
D W
DW
Levy
L S
LS
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000473:pathology*
D015850:Interleukin-6