Effect of dexamethasone on mechanisms responsible for regulation of polyclonal B-cell response.
The effect of dexamethasone (Dex) on the differentiation of pokeweed mitogen (PWM), or Staphylococcus aureus Cowan I (SAC)-stimulated human peripheral blood mononuclear cells (PBMC), into immunoglobulin secreting cells (ISC) was studied with special emphasis on the regulatory role of IL-2 in these systems. Dex, known to reduce endogenous IL-2 production and expression of IL-2 receptors, reduced the proliferation of pokeweed mitogen-activated T-cells, and the proliferation was restored by exogenous recombinant interleukin 2 (rIL-2). Furthermore, Dex enhanced in PWM and in SAC-stimulated cultures, the number of ISC. Addition of rIL-2 resulted in a further increase of ISC in SAC-stimulated cultures, whereas in PWM-stimulated cultures the enhancing effect of Dex was reversed. When IL-2 receptors were blocked by a monoclonal anti-IL-2 receptor antibody rIL-2 was no longer suppressive. Addition of monocytes to PWM-stimulated cultures resulted in suppression or the number of ISC, which was even more pronounced when monocytes were pretreated with rIL-2. In contrast to ISC, neither a suppressive effect of rIL-2 nor an enhancing effect of Dex was observed when PWM-stimulated cultures were evaluated for cells with intracytoplasmic immunoglobulin (plasma cells). From these results we conclude that Dex, by blocking IL-2 production and receptor expression, interferes with IL-2 mediated induction and/or activation of suppressor mechanisms.
Pryjma
J
J
Division of Immunology, Institute of Paediatrics, Copernicus School of Medicine, Cracow, Poland.
Flad
H D
HD
Mytar
B
B
Ennen
J
J
Ernst
M
M
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D007136:Immunoglobulins; D007376:Interleukin-2; D011043:Pokeweed Mitogens; D015375:Receptors, Interleukin-2; D003907:Dexamethasone