Regulation of Fc-induced IL-6 from human peripheral blood mononuclear cells.
Previous experiments demonstrated that aggregated immunoglobulin and the Fc fragment of human IgG can induce interleukin-6 (IL-6) secretion from peripheral blood monocytes. The data herein indicate that Fc-induced IL-6 is modulated by IL-1, IL-4 and interferon (IFN-gamma). When added with Fc fragments, IL-1 and IFN-gamma increased IL-6 production. IL-4 added with Fc fragment did not influence IL-6 production although IL-4 added with LPS was inhibitory to IL-6 production. However, when PBMC were pre-treated with IL-4, IL-4 downregulated Fc-induced IL-6 secretion. The inhibitory effect of IL-4 in the pre-treatment phase could be overcome with a high concentration of IFN-gamma added with the IL-4. Both IL-4 and IFN-gamma acted in a dose- and time-dependent manner. By dot blot analysis, IL-6 mRNA production appeared to be decreased in amount and duration by IL-4 whereas IFN-gamma increased the amount of IL-6 mRNA production. Hence, IL-4 and IFN-gamma appear to have opposing effects and may play a balancing role in the regulation of IL-6 production secondary to Fc exposure.
Ling
Z D
ZD
Department of Paediatrics, University of British Columbia, Vancouver, Canada.
Webb
B T
BT
Yeoh
E
E
Matheson
D S
DS
D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D015342:DNA Probes; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015342:DNA Probes; D007141:Immunoglobulin Fc Fragments; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; D015851:Interleukin-7; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma