Interleukin-4 down-regulates Sendai virus-induced production of interferon-alpha and -beta in human peripheral blood monocytes in vitro.
Recombinant interleukin-4 (rIL-4) caused a 65-70% reduction of the interferon-alpha (IFN-alpha) and -beta production induced by Sendai virus (SV) in human peripheral blood monocytes in vitro. Significant inhibition was seen at concentrations as low as 0.1 ng/ml. The rIL-4 also reduced levels of IFN-alpha and -beta mRNA by 60% and 67%, respectively, as well as the frequency of IFN-alpha and -beta mRNA-containing cells by 65% and 54%, respectively. The frequency of IFN-alpha/beta mRNA-containing cells was inhibited by rIL-4 throughout the whole course of induction by SV. IL-4 caused a shift of the grain count distribution towards less heavily labelled cells, suggesting an inhibitory effect of rIL-4 on most IFN-alpha/beta mRNA-containing cells. Antibodies to rIL-4 did not influence the normal IFN-alpha/beta response induced by SV, but abolished the inhibitory effect of the rIL-4. When rIL-4 was added to cells 4 h after start of stimulation by SV, at which time much mRNA has accumulated but little IFN-alpha/beta has been secreted, no inhibition of the IFN-alpha/beta production by rIL-4 was seen. IFN-gamma had only a minor reversing effect on the rIL-4 inhibition, but if cells were precultivated in medium with or without IFN-gamma for 6 h before SV induction, rIL-4 paradoxically enhanced the IFN-alpha/beta response. Our results suggest that rIL-4 inhibits an early step of IFN-alpha/beta induction in monocytes, at the level either of transcription of IFN-alpha/beta genes or of the processing or stability of mRNA. The IL-4 effects may however depend on the state of activation of the monocytes.
Gobl
A E
AE
Interferon Laboratory, Uppsala University, Sweden.
Alm
G V
GV
D000199:Actins / Q000235:genetics; D015152:Blotting, Northern; D015342:DNA Probes; D015536:Down-Regulation; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008262:Macrophage Activation; D009000:Monocytes / Q000276:immunology*; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000199:Actins; D015342:DNA Probes; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D016899:Interferon-beta; D007371:Interferon-gamma