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Respective effects of soluble interleukin‐1 receptor and tumour necrosis factor receptor on IL‐1 and TNF‐α‐induced DNA synthesis of common acute lymphoblastic leukaemia blasts in vitro
Author(s) -
Carter Anna,
Haddad Nuhad,
Draxler Ilana,
Israeli Ella,
Raz Batya,
Tatarsky Ilana
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb03247.x
Subject(s) - tumor necrosis factor alpha , receptor , antibody , cytokine , microbiology and biotechnology , immunology , alpha (finance) , recombinant dna , biology , interleukin , dna synthesis , in vitro , endocrinology , medicine , biochemistry , gene , construct validity , nursing , patient satisfaction
This study investigates the capacity of human recombinant interleukin‐1α (IL‐1α), IL‐1β and tumour necrosis factor‐α (TNF‐α) to induce DNA synthesis of highly purified blasts from nine adult common acute lymphoblastic leukaemias (cALL) in 7 d liquid culture. IL‐1α, IL‐1β and TNF‐α stimulated 3 H‐TdR uptake in leukaemic blasts in a dose‐dependent fashion. The IL‐1‐induced DNA synthesis of cALL cells could not be prevented by the addition of neutralizing antibodies against IL‐3, GM‐CSF, IL‐6 or TNF‐α. Similarly, the TNF‐α‐stimulated 3 H‐TdR incorporation of leukaemic blasts was not affected by the addition of antibodies towards IL‐1α, IL‐1β, IL‐3, GM‐CSF or IL‐6. These observations suggest that IL‐1 as well as TNF‐α stimulated growth could not be attributed to the endogenous production of factors, corresponding to the antibodies used in these experiments. Both IL‐1 as well as TNF‐α mediate their action through interaction with specific cell surface receptors. Recently two distinct types of IL‐1 receptors (IL‐1‐Rs), IL‐1R (p80) and IL‐1‐R (p65), as well as two distinct types of TNF‐receptors (TNF‐Rs), TNF‐R (p55) and 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 yet 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 while 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 vitro , are functional and interfere with their corresponding cytokine bioactivity.