CYTOKINE-INDUCED SUPPRESSION AND POTENTIATION OF HAPTEN-SPECIFIC IMMEDIATE HYPERSENSITIVITY RESPONSES

The ability of subcutaneously (s.c.) injected cytokines (IL-4, IL-5, I L-6, IFN alpha, IFN gamma, GMCSF) to regulate the induction of hapten- specific immediate hypersensitivity (IH) responses was studied in BPO- KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mi ce at the peak of a hapten-specific IgE antibody forming cell (AFC) re sponse. To induce IH responses, mice were injected in the right pinna with either BPO-BSA (benzylpenicilloyl-bovine serum albumin) , BPO-KLH (0.01-1.0 mug/ml) or mcAb anti-IgE (0.001-1.0 mug/ml) ; and in the le ft pinna with an equal volume of saline (0.05 ml). Pinnae were measure d 5 min to 4 hr later using a micrometer caliper. Treatment of mice wi th IL-4 or IFN gamma dramatically suppressed the induction of IH respo nses in dose dependent fashion. In contrast, treatment of mice with IL -6 and IFN alpha increased these responses in dose dependent fashion, while GMCSF and IL-5 had no effect. The suppression obtained with IL-4 and IFN gamma, and the increases seen with IL-6 and IFN alpha, were t ransient since these cytokines, as well as GMCSF and IL-5, had no effe ct on IH responses elicited 21 days after the peak of BPO-specific IgE AFC responses. The data suggest that cytokine mediated effects on IH responses occur via changes in serum levels of BPO-specific IgGl or Ig E, through direct or indirect effects of cytokines on mast cells or ot her cell types, or by affecting the ability of BPO-specific homocytotr opic antibodies to bind to mast cell surfaces.