Induction of γ‐Interferon by Avarol in Human Peripheral Blood Lymphocytes

Abstract

Avarol is a cytostatic and anti‐human immunodeficiency virus (HIV) agent. In this study, the avarol caused induction of γ‐interferon (IFN‐γ) in buffy coat cells (human peripheral blood lymphocytes) is demonstrated by immunological and molecular biological techniques. IFN‐γ production was detected after a 24‐hr incubation period with avarol; maximal production was obtained after 5 days in the presence of the optimal avarol concentration of 0.75 μg/ml. Blotting experiments using human IFN‐γ cDNA and β‐actin cDNA containing plasmids showed that in the absence of avarol no IFN‐γ transcripts were present in lymphocytes. Already after a 24‐hr incubation with avarol, IFN‐γ gene induction was detected, and maximal induction was found after a 5‐day incubation period. The enhanced IFN‐γ production seems to be caused by a change at the transcriptional and/or post‐transcriptional level, but not during subsequent nucleocyto‐plasmic transport of mRNA. This molecular event is specific, at least in relation to the expression of the β‐actin gene. Our studies demonstrate that avarol displays, besides its potential anti‐tumor and anti‐HIV activity, a potential immunomodulating effect.

Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection

“…Our data show that exogenous addition of these compounds can not restore tumoricidal function. Furthermore, decreased monocyte/macrophage cytotoxicity proceeded depletion ofT4 ~ cells and the reduction of IFN-7 synthesis during the course of HIV-1 disease [45]. While the cells were still able to respond to mitogenic stimulation with a sufficient production of IFN-7, they displayed a loss of cytotoxicity, as detected in a 51Cr-release assay with the same cells as effectors.…”

Marine products as a source of antiviral drug leads

“…Derivatives of these sesquiterpenes were also claimed to be active and have been patented for their antiviral properties [Mueller, 19881. These compounds were further demonstrated to cause T-lymphotrophic cytostatic effect in murine and human lymphocytes and have low in vivo toxicity in mice [Muller et al, 19861. Avarol (12) was able to induce y-interferon in human peripheral blood lymphocytes [Voth et al, 1988).…”