IL-6 ANTISENSE OLIGONUCLEOTIDES INHIBIT IGE PRODUCTION IN IL-4 AND ANTI-CD40-STIMULATED HUMAN B-LYMPHOCYTES

Stimulation of tonsillar B-lymphocytes with CD40 antibodies and IL-4 l eads to homotypic adhesion, proliferation, and differentiation into Ig -producing cells. It also leads to the production of IL-6, a pleiotrop ic cytokine involved in B-cell maturation and differentiation. To asse ss the importance of IL-6 in the differentiation process, an antisense oligonucleotide to IL-6 was added to tonsillar B-cells together with CD40 antibodies and IL-4. This led to clearly reduced levels of IL-6 a s well as to a specific inhibition of IgE production. Also, IgG secret ion was somewhat reduced while IgM appeared to be unaffected. The effe cts were not due to toxicity of the oligonucleotide since proliferatio n proceeded normally or was slightly enhanced in the presence of the a ntisense. The findings show that endogenous IL-6 is an important co-fa ctor for the generation of B-cells secreting IgE and IgG but that it i s not required for IgM production. They further indicate that IL-6 may not be necessary as a co-factor in CD40/IL-4 induced proliferation. ( C) 1998 Elsevier Science B.V. All rights reserved.