Retinoic acid and polyinosinic: Polycytidylic acid synergistically enhance the anti-tetanus IgG response in vitamin A-deficient rats

Vitamin A (VA) deficiency reduces the antibody response to tetanus toxoid (TT), while treatment with retinoic acid (RA) reverses this immunodeficiency. In this study we tested the ability of RA and a potent interferon inducer, polyriboinosinic: polyribocytidylic acid stabilized with poly-1-lysine and carboxymethylcellulose (PIC), alone and in combination, to stimulate the anti-TT IgG response during VA deficiency. Male Lewis rats were fed either a purified VA- free diet (n=24) or were pair-fed the same diet containing adequate VA (n=6). When rats were 41 d old, the 24 VA-deficient rats (serum retinol < 0.2 μmol/L) were divided into four treatment groups: TT only; TT + 3 doses of 100 μg of RA orally beginning on the day of immunization; TT + 20 μg PIC ip on the day of immunization, or TT + both RA and PIC. The pair-fed control group received only TT. Ten d after primary immunization serum anti-TT IgG levels were determined by ELISA. The geometric means of the anti-TT IgG response (in U/ml) were: VA-sufficient, 7.9; VA-deficient, 2.0; RA-treated, 16.6; PIC, 5.3; both, 162.2. By 2-way ANOVA of log-transformed data, there were main effects of RA and PIC (p<0.0001), as well as an interaction (p=0.025). All rats were reimmunized (d 61), without other treatments. The secondary anti-TT IgG response (U/ml) was: VA-suf., 219; VA-def., 18.6; RA, 347; PIC, 30.9; both, 11,749. Main effects and the interaction between RA and PIC were highly significant. These data imply complementarity between the retinoid and cytokine signalling cascades in enhancing IgG production.