RESPECTIVE EFFECTS OF SOLUBLE INTERLEUKIN-1 RECEPTOR AND TUMOR-NECROSIS-FACTOR RECEPTOR ON IL-1 AND TNF-ALPHA-INDUCED DNA-SYNTHESIS OF COMMON ACUTE LYMPHOBLASTIC-LEUKEMIA BLASTS IN-VITRO

This study investigates the capacity of human recombinant interleukin- 1 alpha (IL-1 alpha), IL-1 beta and tumour necrosis factor-alpha (TNF- alpha) to induce DNA synthesis of highly purified blasts from nine adu lt common acute lymphoblastic leukaemias (cALL) in 7 d liquid culture. IL-1 alpha, IL-1 beta and TNF-alpha stimulated H-3-TdR uptake in leuk aemic blasts in a dose-dependent fashion. The IL-1-induced DNA synthes is of cALL cells could not be prevented by the addition of neutralizin g antibodies against IL-3, GM-CSF, IL-6 or TNF-alpha. Similarly, the T NF-alpha-stimulated H-3-TdR incorporation of leukaemic blasts was not affected by the addition of antibodies towards IL-1 alpha, IL-1 beta, IL-3, GM-CSF or IL-6. These observations suggest that IL-1 as well as TNF-alpha stimulated growth could not be attributed to the endogenous production of factors, corresponding to the antibodies used in these e xperiments. Both IL-1 as well as TNF-alpha mediate their action throug h interaction with specific cell surface receptors. Recently two disti nct types of IL-1 receptors (IL-1-Rs), IL-1R (p80) and IL-1-R (p65), a s well as two distinct types of TNF-receptors (TNF-Rs), TNF-R (p55) an d TNF-R (p75) have been identified. Both types of TNF-Rs exist also in soluble forms (sTNF-Rs), while soluble IL-1-Rs (sIL-1-Rs) have not ye t been found naturally. In this study we show that sIL-1-R as well as sTNF-R modulate the effects of their corresponding cytokine in a dose- dependent bimodal fashion; at lower concentrations they augmented whil e at higher concentrations they inhibited the cytokine-stimulated DNA synthesis of cALL blasts in vitro. It may therefore be concluded from this study that soluble receptors for both IL-1 and TNF, at least in v itro, are functional and interfere with their corresponding cytokine b ioactivity.