Hydrocortisone-mediated inhibition of monocyte antigen presentation: dissociation of inhibitory effect and expression of DR antigens.
The suppressive effects of hydrocortisone (HC) on the human immune system are well known. The mediation of the immunosuppressive effects of HC on lymphocyte responses via inhibition of monocyte function has been examined by monocyte-dependent, antigen-induced lymphocyte proliferation. Monocytes that were first treated with HC and then washed were unaffected in their subsequent ability to present antigen. However, there was a dramatic inhibition of lymphocyte proliferative responses if HC was present while monocytes were pulsed with antigen. This was directly related to the dose of HC present. HC-mediated inhibition of monocyte antigen presentation could not be overcome by the addition of interleukin-1 (IL-1) to cultures, and thus inhibition of monocyte IL-1 secretion cannot totally account for the inhibition of monocyte antigen presentation. Although HC inhibits monocyte antigen presentation, HC increases the expression of HLA-DR antigens on monocytes. Other monocyte stimulants, including lipopolysaccharide (LPS), lymphokine, and gamma interferon, were examined for their effect on monocyte DR expression and their effect on monocyte antigen presentation. No correlation was found between the ability to increase monocyte DR antigen expression and the effect on antigen presentation. While HC, lymphokine, and gamma interferon all increased the expression of DR antigens on monocytes, HC, LPS, and lymphokine, but not gamma interferon, inhibited monocyte antigen presentation. Although HC can exert profound immunosuppressive effects via monocytes, it is not the only mechanism of inhibition. HC added to cultures after monocytes had been pulsed with antigen was also inhibitory.
D000941:Antigens / Q000276:immunology; D006684:HLA-DR Antigens; D006433:Hemocyanins; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008222:Lymphokines; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D006854:Hydrocortisone