A HIGHLY SENSITIVE QUANTITATIVE BIOASSAY FOR HUMAN INTERLEUKIN-11

Human interleukin-11 (IL-11) is a cytokine with a broad spectrum of ac tivity, similar to interleukin-6 (IL-6). However, its role in human di sease is poorly understood, partly because of a lack of sensitive bioa ssays. A subclone (B9-11) obtained from the B9 hybridoma (which respon ds poorly to human IL-11) enabled us to develop a highly sensitive bio assay for human IL-11. B9-11 cells responded only to human IL-11 and I L-6 and not to other human cytokines using the same gp130 transducer c hain (ciliary neurotrophic factor, leukemia inhibitory factor and onco statin M) or to other human interleukins (interleukin-1 to interleukin -13), human hematopoietic cytokines (granulocyte colony stimulating fa ctor, granulocyte-macrophage colony stimulating factor, colony stimula ting factor-1) and various other human cytokines (interferon-alpha, tu mor necrosis factor-alpha, tumor necrosis factor-beta, fibroblast grow th factor and nerve growth factor). In addition, these cytokines did n ot interfere with the IL-11 response of B9-11 cells. IL-11-induced pro liferation of B9-11 cells was unaffected by anti-murine IL-6 receptor mAb but inhibited by anti-gp130 mAb. Half-maximal proliferation of B9- 11 cells was obtained with 30 pg/ml of recombinant IL-11, a concentrat ion 300-fold lower than IL-11 concentrations known to be active on hum an cells. Finally, culturing of B9-11 cells with an anti-IL-6 mAb enab led us to measure the natural IL-11 produced by various cell lines. Th us, B9-11 cells should be useful for studies of IL-11 involvement in v arious human diseases as well as for a better understanding of the mec hanisms of action of this cytokine.