Response of microvascular endothelial cells to biological response modifiers

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; alpha and gamma), tumour necrosis factor (TNF; alpha and beta), transforming growth factor (TGF; alpha and beta), rIL-1, rIL-2, pIL-2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rIL-2 (greater than or equal to 10 U/mL) caused proliferation of the cells. gamma IFN together with TNF alpha(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: alpha or gamma IFN (greater than or equal to 1000 U/mL), TGF beta (greater than or equal to 5 ng/mL), rIL-1 (greater than or equal to 0.5 U/mL) and rIL-1 plus gamma IFN. gamma IFN (500 U/mL) plus TNF alpha exhibited synergism in the inhibition of proliferation and produced a cytotoxic effect at TNF alpha concentrations greater than or equal to 500 U/mL. By contrast, rIL-2 enhanced proliferation at greater than 5 U/mL. When rIL-2 was combined with gamma IFN, an inhibitory effect on proliferation was observed, although to a lesser extent than gamma IFN alone. Pretreating the cells with 100 U/mL gamma IFN prior to rIL-1 or IL-2 exposure produced no change in the trends observed above.(ABSTRACT TRUNCATED AT 250 WORDS)