Endogenous anxiogenic peptide, ODN-diazepam-binding inhibitor, and benzodiazepines enhance the production of interleukin-1 and tumor necrosis factor by human monocytes.

Benzodiazepines (BZD) have been described to interact with specific peripheral-type receptors on phagocytes. The present study demonstrates that pico- to nanomolar concentrations of BZD compounds enhance the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by human monocytes, as determined by specific immunoreactive and biological assays for these cytokines. BZD remained ineffective in the absence of LPS. The activity of BZD was restricted to peripheral (Ro 5-4864) and mixed (diazepam, Valium) type ligands, while anxiogenic (beta-carbolines) or anxiolytic (clonazepam) central type ligands had no effect. Interestingly, peptide fragments of the endogenous anxiogenic ligand diazepam-binding inhibitor (DBI), such as octadecaneuropeptide (ODN-DBI) and the octaneuropeptide corresponding to its COOH-terminal sequence, very efficiently modulated the LPS-induced production of both monokines. Similar results were obtained directly within whole blood samples. These results indicate that widely prescribed pharmacological compounds and endogenous anxiety modulators affect molecular mediators of human host defense mechanisms and inflammatory reactions.