Abstract
The immunomodulator OHR/AVR118 has been shown to increase IL-8 and MCP-1 secretion from non-activated human monocytes and U937 pro-monocytic cells, but to decrease MCP-1 secretion from LPS-activated monocytes, suggesting its effect depends on immune cell environment and/or activation state. We therefore assessed the effect of OHR/AVR118 on cytokine secretion by human PBMCs and adherent monocytes. OHR/AVR118 increased IL-6, IL-1β, and TNF-α secretion byPHA/IL-2-primed PBMCs, but did not alter IL-12 secretion. In contrast, treatment of LPS-activated monocytes decreased TNF-α and IL-12, increased IL-6, but did not alter IL-1β, secretion. To further show that the effect of OHR/AVR118 depends on cellular environment, we monitored U937 differentiation towards mature macrophages in the presence of drug. OHR/AVR118 promoted a pro-inflammatory response in PMA-activated cells, as demonstrated by increased expression of the maturation markers CD86, CD32, and CD87 and by increased IL-8, MCP-1, and GM-CSF secretion. In undifferentiated U937 cells, OHR/AVR118 did not alter phagocytosis of opsonized S. aureus and IL-10 secretion. Whereas, after activation, OHR/AVR118 induced an anti-inflammatory phenotype, as indicated by reduced phagocytosis and increased IL-10 secretion. Overall, these findings suggest that OHR/AVR118 has a dual action on monocyte/macrophage function depending on cellular activation state, resulting in either further activation or suppression.
Highlights
OHR/AVR118 is a novel immunomodulator containing a 31-amino acid peptide and a 21-residue peptide nucleic acid, in which a diadenosine is covalently attached to serine-18 via a phosphodiester bond [1]
The immunomodulator OHR/AVR118 has been shown to increase IL-8 and MCP-1 secretion from non-activated human monocytes and U937 pro-monocytic cells, but to decrease MCP-1 secretion from LPS-activated monocytes, suggesting its effect depends on immune cell environment and/or activation state
After activation, OHR/AVR118 induced an anti-inflammatory phenotype, as indicated by reduced phagocytosis and increased IL-10 secretion. These findings suggest that OHR/AVR118 has a dual action on monocyte/macrophage function depending on cellular activation state, resulting in either further activation or suppression
Summary
OHR/AVR118 (previously called Product R) is a novel immunomodulator containing a 31-amino acid peptide and a 21-residue peptide nucleic acid, in which a diadenosine is covalently attached to serine-18 via a phosphodiester bond [1]. OHR/AVR118 is chemically stable and has a favorable safety profile, both in animal toxicity studies and in human clinical trials [2]. Results of Phase 1 and early Phase 2 clinical trials indicate that OHR/ AVR118 has efficacy in treating anorexia and cachexia in severely ill patients [2,3,4]. We demonstrated previously that OHR/AVR118 increases IL-8 and MCP-1 secretion by non-activated human monocytes and U937 pro-monocytic cells, but decreases MCP-1 secretion by LPS-activated monocytes [5]. These findings suggested that the effect of OHR/AVR118 on immune cells is dependent on cellular environment and/or activation state
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
