The purpose of this study was to determine the influence of recombinant human interleukin-4 (IL-4) on the regulation of lymphokine-activated killer (LAK) and mixed lymphocyte culture cytotoxic activity. Lymphocytes from several lymphoid tissues were studied including human peripheral blood leukocytes (PBL), spleen cells, thymocytes, and thoracic duct lymphocytes. Cells were cultured with IL-4 in the presence or absence of recombinant human interleukin-2 (IL-2) in 4-day cultures. LAK and natural killer (NK) activities were measured in a standard chromium release cytotoxicity assay against LAK-sensitive, NK-resistant M14 melanoma targets and NK-sensitive K562 erythroleukemic cells. IL-4 alone does not increase NK or LAK activity under the conditions studied. However, IL-4 does inhibit the induction of cytotoxic activity by IL-2. IL-4 inhibits IL-2-induced thymidine incorporation in 3-day PBL cultures, suggesting that the inhibition of cytotoxicity is not a dilution effect due to the proliferation of noncytotoxic cell populations. IL-4 also inhibits the development of LAK and NK-like activities generated in mixed lymphocyte culture (MLC) while augmenting MLC-generated allospecific cytotoxic T lymphocyte activity. Thus, IL-4 appears to inhibit the induction of nonspecific cytotoxic effectors while augmenting the generation of MHC-specific responses. This confirms an important regulatory function for this lymphokine in the generation of cytotoxic effectors.
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