Interferon‐γ‐ and interleukin‐4‐targeted gene therapy for atopic allergic disease

Two cytokines, interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4), which play critical roles in the regulation of serum IgE level by directing the interplay of T helper (Th)1 and Th2 cells, were chosen as targets for gene therapy. Anti‐allergic activity was evaluated by determining the serum IgE level, and the functional status of each helper T cell was monitored by the serum concentrations of IgG1 and IgG2a. Experimental animals (BALB/c mice) were divided into four groups: the control group; the ovalbumin (OVA) group; the IFN‐γ group; and the IL‐4 group. The control group was injected with saline and the OVA group with OVA–alum. The IFN‐γ and IL‐4 groups were treated with OVA–alum plus the cDNAs of mouse IFN‐γ and IL‐4 in an expression vector. These treatments were applied intramuscularly on a monthly basis for 4 months. OVA–alum treatment significantly increased the serum IgE and IgG1 concentrations, but did not affect IgG2a. Concomitant treatments with the cDNA of IFN‐γ or IL‐4 returned the serum IgE almost to the control level and significantly suppressed the OVA‐induced increase of IgG1. IFN‐γ cDNA increased the serum IgG2a but IL‐4 cDNA had no affect. These results suggest that IFN‐γ inhibited the OVA‐induced IgE production by suppressing the Th2 pathway and by enhancing the Th1 pathway. Administration of IL‐4 cDNA suppressed the OVA‐induced enhancement of IgE production by inhibiting the Th2 pathway rather than by potentiating it.