Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone.
Glucocorticoids are extremely potent immunosuppressive agents, capable of directly affecting the function of lymphocytes. We studied the effect of in vivo dexamethasone (DEX) administration on anti-CD3-induced lymphocyte proliferation and lymphokine production in mice. To characterize the kinetics and dose responsiveness of lymphocytes to DEX, splenocytes from BALB/c mice that had received a single dose of DEX in vivo were cultured in vitro with suboptimal and optimal concentrations of anti-CD3 monoclonal antibody. Cell proliferation in response to suboptimal concentrations of anti-CD3 was decreased by DEX doses of > or = 30 mg/kg; much higher doses (> or = 200 mg/kg) were required to inhibit cell proliferation in response to optimal anti-CD3 stimulation. Inhibition of suboptimal anti-CD3-stimulated proliferation was evident within 4 hr after DEX administration, was maintained for at least 24 hr, and was no longer evident at 7 and 14 days. Lymphokine secretion induced by optimal doses of anti-CD3 in vitro was differentially affected by in vivo DEX treatment. IL-1 alpha, IL-4, IL-6, IL-10, and IFN-gamma levels were decreased by treatment with low doses of DEX (30 mg/kg), whereas higher doses were required to inhibit production of IL-2, IL-3, and TNF. GM-CSF (granulocyte-macrophage-colony stimulating factor) was least susceptible to DEX inhibition. Low-dose (30 mg/kg) DEX treatment significantly reduced anti-CD3-stimulated production of most lymphokines tested at 4 and 12 hr; by 24 hr the levels of most lymphokines had begun to return to control values. Hence, our data indicate that administration of a single dose of DEX (30 mg/kg for 4 hr) results in significant suppression of lymphokine production and cell proliferation that precedes any significant cell loss and can be used as a reversible model of immunosuppression.
Kunicka
J E
JE
Immunobiology Research Institute, Annandale, New Jersey 08801.
Talle
M A
MA
Denhardt
G H
GH
Brown
M
M
Prince
L A
LA
Goldstein
G
G
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D008222:Lymphokines; D003907:Dexamethasone