Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood mononuclear cells in response to viral stimulation.
IL-10 is an important regulator of the production of proinflammatory cytokines. Its effect on IFN-alpha production, however, has not been reported. In this study, PBMC from healthy donors were stimulated with virus in the presence of IL-10. Human IL-10 (hIL-10) caused reductions in both the frequency of IFN-alpha-producing cells (IPC) and bulk IFN in response to herpes simplex virus type-1 (HSV-1), Sendai virus, Newcastle disease virus, and vesicular stomatitis virus. The inhibitory effect occurred when IL-10 was added 2 or 4 h before, or 2 h poststimulation with HSV or Sendai virus, but not when added 4 h postinduction. Unlike IL-10, IL-4 did not affect the IFN-alpha response to HSV. However, when PBMC were induced with Sendai virus, IFN-alpha production was also reduced by IL-4. IL-10 treatment of PBMC resulted in strong reductions in the steady state levels of both HSV- and Sendai virus-induced IFN-alpha1, -alpha2, and -beta mRNA as determined by RT-PCR. IFN-alpha production to Sendai virus occurs predominantly by monocytes, whereas most enveloped viruses stimulate low frequency "natural IFN-producing cells (NIPC)," which are thought to be dendritic cells. Peripheral blood dendritic cells were found to express the IL-10 receptor, suggesting that IL-10 may directly act on the dendritic IPC. Addition of monoclonal anti-IL-10 to PBMC resulted in a significant increase in both the frequency of IPC and the amount of secreted IFN-alpha in response to HSV but not Sendai virus. We conclude that human IL-10 can serve as both an endogenous and exogenous regulator of IFN-alpha production.
Payvandi
F
F
Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
Amrute
S
S
Fitzgerald-Bocarsly
P
P
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D018259:Herpesvirus 1, Human; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D009522:Newcastle disease virus; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D018108:Respirovirus; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus
D016898:Interferon-alpha; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D015847:Interleukin-4; D016899:Interferon-beta