Prostaglandin-mediated inhibition of lymphokine secretion in normal individuals and patients with progressive systemic sclerosis (scleroderma, PSS).
The sensitivity of peripheral blood lymphocytes to E-type prostaglandin-mediated inhibition of lymphokine secretion was examined in 3 groups of individuals; normal controls, hospitalized patients, and patients with progressive systemic sclerosis (PSS, scleroderma). Leukocytes were stimulated by a polyclonal T-cell activator, phytohemagglutinin, and the release of the lymphokine, leukocyte migration inhibitory factor (LIF), was measured in the presence or absence of exogenous PGE2 using a direct agarose droplet migration inhibition technique. Leukocytes of scleroderma patients were found to be hyporesponsive to E-type prostaglandin (i.e., lymphokine secretion by these cells was not inhibited at concentrations of PGE2 between 2.8 X 10(-8) and 2.8 X 10(-5) M). In addition, a marked sex difference in PGE responsiveness was found to exist among normal controls, whereby females were hyporesponsive during the latter half of the menstrual cycle. It is possible that this deficit may facilitate, in part, the development of connective tissue diseases in women of childbearing age. The inability to suppress lymphokine production and arrest persistent immune reactivity, coupled with the known ability of lymphokines to augment fibroblast collagen production, offers a a reasonable explanation for the accumulation of tissue collagen in scleroderma.
D000328:Adult; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism*
D008222:Lymphokines; D010835:Phytohemagglutinins; D011453:Prostaglandins; D011458:Prostaglandins E; D000242:Cyclic AMP; D015232:Dinoprostone