Abstract:
:The biological response modifier OK-432 has been shown both to exert the enhancement of several immunological activities and to have a direct anti-tumor effect. The present study examines the immunopotentiating effect of OK-432 on peripheral blood monocytes (PBM) derived from normal humans. Monocyte activation was assessed by examining direct cell-mediated cytotoxic activity (CMC) and secretion of cytotoxic factors in the supernatant by the 51Cr release assay and secretion of tumor necrosis factor (TNF)-alpha detected by a sensitive radioimmunoassay. The OK-432-augmented activity was compared to that achieved by recombinant interferon-gamma (rIFN-gamma). Coculture of PBM with OK-432 overnight resulted in significant augmentation of CMC and secretion of cytotoxic factors and TNF in the supernatant. The effects observed were dose dependent and the resulting activity was much more pronounced than that achieved with an optimal concentration of IFN-gamma. The monocyte- and supernatant-mediated cytotoxic activities were in a large part attributed to TNF as both activities were inhibited by anti-TNF antibody. Several parameters of monocyte activation by OK-432 were examined. The kinetics of monocyte activation revealed that a short time exposure (2-6 hr) was sufficient for activation but maximal activation was detected after 18 hr. However, the kinetics of the cytotoxic assay were not shortened and 16-20 hr was necessary for optimal cytotoxic activity. Significant synergy was obtained when suboptimal concentrations of OK-432 and IFN-gamma were used. The synergy was noted in CMC, supernatant activity, and TNF concentration. These results demonstrate that OK-432 is a potent activator of monocyte cytotoxicity and also activates secretion of TNF. Also, OK-432 is a much more potent activator than rIFN-gamma. The synergy with OK-432 and IFN-gamma suggests that OK-432-mediated activation of monocytes takes place by a different mechanism than that mediated by rIFN-gamma. Thus, monocytes and products thereof may actively participate in the in vivo anti-tumor effect mediated by OK-432.
journal_name
Cell Immunoljournal_title
Cellular immunologyauthors
Bonavida B,Jewett Adoi
10.1016/0008-8749(89)90297-9subject
Has Abstractpub_date
1989-10-15 00:00:00pages
373-83issue
2eissn
0008-8749issn
1090-2163pii
0008-8749(89)90297-9journal_volume
123pub_type
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