Systemic delivery of an adenovirus expressing EBV-derived vIL-10 in mice infected with Schistosoma mansoni or Leishmania amazonensis: controversial effects on the development of pathological parameters

Within the context of microorganism/host interactions, those which last ove r weeks are expected to be sensitive to more or less sustained and targeted immuno-intervention, such as delivery of cytokines known to operate as dow n-regulators of acute inflammatory processes. IL-10 has received growing at tention as a potential tool in immunotherapy, due to its anti-inflammatory and immunosuppressive properties, Therefore, using two experimental models of long-term interactions between parasites and laboratory mice, we monitor ed some effects of the systemic delivery of an adenovirus (Ad) expressing E BV-derived IL-10 (vIL-10) designated Ad-vIL-10, We first monitored the vIL- 10 serum level following intranasal, intraperitoneal, intramuscular and int ravenous administration. The i.p. and i.v. delivery of Ad-vIL-10 allowed a high serum level of vIL-10 (= 100 ng/ml), the i.v. route leading to a more sustained expression (up to 3 weeks). As a first model of parasite/mouse in teraction, Schistosoma mansoni/C57Bl/6 mouse was selected. Ad-vIL-10 delive ry was performed 4 weeks after S. mansoni infection i.e. at the time of egg -laying, and several parameters mere monitored: (i) number of adult worms i n the mesenteric vein, (ii) number of eggs trapped in the liver and intesti ne, (iii) liver fibrosis, (iv) serum levels of egg-reactive antibody subcla sses, (v) serum content of cytokines, and (vi) cytokine production in the s upernatant of antigen-stimulated mesenteric lymph node cells. No apparent e ffect was observed, either on the different parasitological parameters or o n fibrosis development at day 70 of infection. Surprisingly, a marked incre ase in both Th1 and Th2 type cytokines was observed in the sera of the Ad-v IL-10 injected animals, as well as in the supernatants of their Ag-stimulat ed mesenteric lymph node cells. Nevertheless, polarization of the humoral r esponse towards a Th2 profile was demonstrated by an increase in the IgE le vel in the Ad-vIL-10-injected animals. As far as the second model is concer ned, namely the Leishmania amazonensis /C57Bl6 mouse interactions, Ad-vIL-1 0 was delivered intravenously one day before subcutaneous injection of stat ionary promastigotes and footpad swelling was monitored over 110 days. Unde r these conditions, vIL-10 exhibited a biphasic effect, decreasing the lesi on size at the early stages of infection, but leading to a more pronounced lesion size during the chronic phase. This observation suggests a deactivat ion of the macrophage host cells under the influence of vIL-10, The results are discussed in the context of immunotherapy and the paradoxical effects observed in immunointervention with vIL-10.