Direct and mononuclear cell mediated effects on interleukin 6 production by glioma cells in infection with herpes simplex virus type 1

J Med Virol. 2001 Mar;63(3):252-8. doi: 10.1002/1096-9071(200103)63:3<252::aid-jmv1009>;2-e.


To clarify the mechanism of interleukin (IL)-6 elevation in the cerebrospinal fluid of viral meningitis and/or encephalitis patients, we investigated how herpes simplex virus type 1 (HSV1)-infection enhances IL-6 production in human glioma cells (the U373MG and T98G cells). Although human glioma cells did not show enhanced IL-6 production by direct HSV1-infection, the cell-free supernatant from HSV1-stimulated mononuclear cells (MNC) culture and lipopolysaccharide, as a positive control, markedly elevated IL-6 production at both mRNA and polypeptide levels. Ultra violet-irradiated HSV1 induced the secretion of the IL-6 inducing factor(s) from MNC, whereas heat-inactivated HSV1 did not show this activity. This finding indicated that the adsorption of virus on the surface of MNC may be sufficient for induction of secretion. The supernatant from the culture of HSV1-stimulated MNC contained detectable amounts of IL-1beta, tumor necrosis factor (TNF) alpha, interferon (IFN) gamma and IL-6, and its IL-6-inducing activity was inhibited only by anti-IL-1beta antibodies. Moreover, recombinant IL-1beta markedly enhanced IL-6 production in glioma cells with a concomitant elevation of its mRNA level. Taken together, the results suggest that in HSV1-infection of the CNS, enhancement of IL-6 production in glial cells is mediated not by direct infection to glial cells but rather by IL-1beta released from HSV1-stimulated MNC. These findings may help elucidate the mechanisms underlying cerebro-parenchymal inflammatory progression and repair in herpes simplex encephalitis.

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Culture Media, Conditioned
  • Encephalitis, Viral / metabolism
  • Glioma
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Interleukin-1 / physiology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Leukocytes, Mononuclear / physiology*
  • Meningitis, Viral / metabolism
  • Neuroglia / metabolism*
  • RNA, Messenger / biosynthesis
  • Tumor Cells, Cultured
  • Vero Cells


  • Culture Media, Conditioned
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger