Characteristics of interleukin-6-enhanced lymphokine-activated killer cell function.
To study the effect of IL-6 on the development of cytotoxic cells, we examined lymphokine-activated killer (LAK) activity generated from human nonadherent PBL. Addition of rIL-6 at the initiation of 5-day PBL cultures significantly increases LAK activity in the presence of low concentrations (between 5 and 25 u/ml) of rIL-2. RIL-6 alone induces no PBL LAK activity but at doses as low as 0.8 u/ml rIL-6 enhances LAK activity with optimal enhancement of LAK at 5.0 u/ml of rIL-6. This enhancement is independent of effects on cells growth as rIL-6 did not affect the cell recovery of PBL cultured in rIL-2. RIL-6-enhanced LAK is mediated by the same type of effector cells as those of LAK from rIL-2 alone with effector cells primarily generated from large granular CD3-negative E rosetting lymphocytes. RIL-6 does not change the time course of LAK development and pretreatment of PBL with rIL-6 has no effect on the PBL response to subsequent rIL-2 induction of LAK. Addition of rIL-6 to LAK cultures 2 hr before the cytotoxicity assay shows equal enhancement as addition at the initiation of the culture. However, rIL-6 requires the presence of both rIL-2 and another factor in the supernatant from LAK cultures in order to enhance LAK. Our results indicate that IL-6 can modulate LAK activity at a very late stage of LAK development, and that the enhancement by IL-6 is dependent on the presence of IL-2 and another soluble factor generated during rIL-2 culture.
Iho
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Division of Surgical Oncology, UCLA School of Medicine 90024.
Shau
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Golub
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SH
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins