Modulation of the IL-2 production defect in vitro in Graves' disease.
IL-2 production by mitogen-induced peripheral blood mononuclear cells was reported to be reduced in several autoimmune diseases, including Graves' disease (GD). This production defect in hyperthyroid GD was restored to normal by antithyroid drug therapy or during remission. However, its underlying mechanism and role in the autoimmune process are still uncertain. The present study was undertaken in order to screen the in vitro IL-2 generating system for putative factors responsible for its failure, and to see to what extent this was reversible. Thyroid hormone or antithyroid drugs had no effect on IL-2 production in vitro. Cultures were found to be free of soluble inhibitors of IL-2 production or action. IL-1 deficiency as a cause of the IL-2 defect was ruled out; rather, Graves' adherent cells were found to be activated in being capable of secreting large amounts of IL-1 and prostaglandin E2 (PGE2). The latter was not found to be responsible for the decreased IL-2 production. IL-2 production by Graves' mononuclears was completely restored to normal by: (i) adherent cell depletion, irradiation or substitution with normal adherent cells; (ii) preincubation of mononuclears for 24-72 h before mitogen stimulation; (iii) the synergistic action of a phorbol ester and a calcium ionophore. These data indicate that inhibition by activated adherent cells accounts for the in vitro IL-2 production defect in GD. This inhibition is not mediated by soluble factors, but probably through direct interaction with the producing cells, and is reversible in rested cultures or through a bypassed signal transduction.
Eisenstein
Z
Z
Department of Medicine, Sheba Medical Centre, Tel-Hashomer, Israel.
Engelsman
E
E
Weiss
M
M
Kalechman
Y
Y
Sredni
B
B
D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006111:Graves Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D009915:Orbit / Q000276:immunology*; D011441:Propylthiouracil / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D014284:Triiodothyronine; D008713:Methimazole; D011441:Propylthiouracil; D013755:Tetradecanoylphorbol Acetate