Response of microvascular endothelial cells to biological response modifiers

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Abstract
This study investigated in vitro biological response modifiers (BRM) possibly involved in initiation and regulation of human capillary endothelial cell (HCEC) growth. An indicator assay was developed using tritiated thymidine to measure increased DNA turnover. Purified or recombinant BRMs tested singly and in combination included: interferon (IFN; and ), tumour necrosis factor (TNF; and ), transforming growth factor (TGF: and ). rIL-1, rIL-2, pIL-2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rlL-2 ( 10 U/mL) caused proliferation of the cells. IFN together with TNF(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: or IFN ( 1000 U/mL), TGF (5 ng/mL), rIL-1 ( 05 U/mL) and rIL-1 plus IFN, IFN (500 U/mL) plus TNF exhibited synergism in the Inhibition of proliferation and produced a cytotoxic effect at TNF concentrations 500 U/mL. By contrast, rIL-2 enhanced proliferation at >5 U/mL. When rIL-2 was combined with IFN, an inhibitory effect on proliferation was observed, although to a lesser extent than IFN alone. Pretreating the cells with 100 U/mL IFN prior to rIL-1 or IL-2 exposure produced no change in the trends observed above. TGF also stimulated cell proliferation at concentrations 05 ng/mL. PDGF and retinoic acid had no effect on proliferation in the concentration range 05-10 U/mL. By investigating the response of HCEC to these BRMs, the nature of, and response to the signals from immune cells in inflammatory disease processes can be better understood.