Selective inhibition of excessive scleroderma fibroblast collagen production by lymphokines from normal human mononuclear cells.
We studied the effects of lymphokines from mitogen-stimulated normal human mononuclear cells on collagen production by confluent monolayer cultures of scleroderma dermal fibroblasts. We examined 10 cell lines obtained from patients with early onset, rapidly progressive disease. All cell lines exhibited increased collagen production, compared with cell lines from age- and sex-matched normal individuals. We found that supernatants from phytohemagglutinin-stimulated mononuclear cells caused greater than 45% inhibition of collagen production by the cultured scleroderma fibroblasts; the degree of inhibition was concentration-dependent. Partially purified lymphokine preparations produced 84-94% inhibition of collagen production by scleroderma cells. The lymphokine effects were shown to be selective for collagen, since the synthesis of noncollagenous proteins was not significantly affected. The results suggest that lymphokines from normal mononuclear cells can modulate the excessive collagen biosynthesis that is characteristic of scleroderma fibroblasts, and these lymphokines may have a place as possible therapeutic agents for this incurable disease.
D000328:Adult; D000368:Aged; D002460:Cell Line; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
D008222:Lymphokines; D005643:Fucose; D014443:Tyrosine; D003094:Collagen