Interferon induction by SMANCS: A polymer-conjugated derivative of neocarzinostatin

Poly (styrene-co-maleic acid)-conjugated neocarzinostatin, SMANCS, induced antiviral activities in the circulation of mice. The maximum titer of the activity (240 U/ml) was observed 20 h after administration of an 8 mg/kg iv dose of SMANCS. Various experiments showed that this antiviral substance induced by SMANCS was an interferon (IFN). Sixty percent of IFN response stimulated by SMANCS was impaired in mice pretreated with anti-IFNγ antiserum. This suggests that the serum IFN induced by the agent contained about 60% of IFNγ. When Thy 1+ or Lyt 2+ T-cells were depleted from mice by administration of anti-Thy 1.2 or anti-Lyt 2.2 monoclonal antibody (mAb), this IFN response was eliminated. However, when natural killer cells were depleted from mice by treatment with antiasialo GM1 antiserum, no alteration in the IFN response was observed. The SMANCS-stimulated IFN response was also abrogated in mice treated with macrophage (MΦ) blockers (carrageenan and trypan blue), whereas administration of anti-Lyt 1.2 mAb had no effect on the IFN response. These results suggest that MΦ and T-cells with Lyt 1-2+ phenotype may have an important role in the IFN response stimulated by SMANCS.