Regulatory effects of IL-12 and IL-18 on Onchocerca volvulus- and Entamoeba histolytica-specific cellular reactivity and cytokine profiles

Parasite Immunol. 2003 Jun;25(6):325-32. doi: 10.1046/j.1365-3024.2003.00638.x.


In the present study, the cytokines interleukin (IL)-12 and IL-18 were evaluated for their capacity to modulate and to re-direct in vitro parasite antigen-specific cellular responsiveness in patients exposed to Onchocerca volvulus and Entamoeba histolytica infection. We found that IL-18 was highly capable of reducing parasite antigen-induced IL-10 production by PBMC. In contrast, addition or neutralization of IL-12, also in combination with IL-18 and the interferon-gamma-inducible chemokine IP-10 did not affect IL-10 production. Interestingly, the highest IL-10 levels were measured when IL-18 and IP-10 were both neutralized. Although having no effect on IL-10, IL-12 strongly promoted spontaneous and parasite antigen-driven IFN-gamma production by PBMC, whereas IL-18 was only moderately affecting IFN-gamma release by PBMC re-stimulated with E. histolytica- or O. volvulus-specific antigens. Both IL-12 and IL-18 diminished the cellular production of IL-13, and a synergistic effect was observed when the cytokines were combined. Likewise, neutralization of IL-12 enhanced Entamoeba and Onchocerca antigen-driven IL-13 production, but no further increase of IL-13 was observed, when anti-IL-12 and anti-IL-18 were used together. This study disclosed that IL-18 will significantly down-regulate parasite-specific IL-10 production, whereas IL-12 induced IFN-gamma and inhibited IL-13 production by PBMC from humans exposed to O. volvulus and E. histolytica. Such selective immune-regulatory capacity of IL-12 and IL-18 may comprise an important tool to re-direct polarized cytokine responses towards a balanced Th1/Th2 cytokine profile, which may prevent pathology and promote immunity against helminth and protozoan parasite infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Helminth / immunology
  • Chemokine CXCL10
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / immunology
  • Entamoeba histolytica / immunology*
  • Entamoebiasis / blood
  • Entamoebiasis / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology*
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / immunology*
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Middle Aged
  • Onchocerca volvulus / immunology*
  • Onchocerciasis / blood
  • Onchocerciasis / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antigens, Helminth
  • Chemokine CXCL10
  • Chemokines, CXC
  • Interleukin-18
  • Interleukin-5
  • Interleukin-10
  • Interferon-gamma