THE LOCAL LYMPH-NODE ASSAY - AN INTERLABORATORY EVALUATION OF INTERLEUKIN-6 (IL-6) PRODUCTION BY DRAINING LYMPH-NODE CELLS

The murine local lymph node assay is a predictive method for the ident ification of skin-sensitizing chemicals in which activity is measured as a function of proliferative activity induced in lymph nodes drainin g the site of exposure. In the present study, the induction by topical ly applied chemicals of draining lymph node cell (LNC) production of t he cytokine interleukin 6 (IL-6) has been evaluated as an alternative endpoint for the local lymph node assay. In addition, results derived from studies of IL-6 production by LNC performed independently in two separate collaborating laboratories have been compared. Of the nine sk in sensitizing chemicals examined, six provoked detectable levels (>15 0 pg ml(-1)) of IL-6 production by draining LNCs (as measured by enzym e-linked immunosorbent assay) following exposure of mice to at least o ne test concentration of the material in both of the laboratories. Thr ee other sensitizing chemicals failed to induce measurable IL-6 produc tion at any test concentration in either one or both of the participat ing laboratories, Both of the non-sensitizing chemicals evaluated (sod ium lauryl sulphate and methyl salicylate) also failed to result in de tectable IL-6 synthesis. There was a high level of agreement between t he two laboratories. The rank order of chemicals with respect to IL-6 production by LNCs was identical in both cases, as was the dose-respon se relationship observed with each test material. These data reveal th at, although inducible IL-6 production by draining LNCs provides a rob ust approach to the measurement of strong sensitizing activity, as per formed here the method is of insufficient sensitivity for the routine identification of skin allergens.