ABSTRACT
Our studies on the seleno-organic compounds were focused at their activities as the modest cytokine inducers in human peripheral blood leukocyte cultures. Our bioassays used in the screening methods were based on the quantitative determinations of mainly two types of cytokines: interferons (IFNs) and tumor necrosis factors (TNFs). More recently we have found that several of the compounds have direct immunotropic actions in vitro and in vivo, in mice and in chickens. The paper summarizes the data related to the cytokine-inducing activity of 65 seleno-organic compounds divided into 4 groups according to their chemical structures. The reference compound was ebselen, the well known experimental drug with various biological activities. Approximately 50% of the compounds were found to be active in our bioassays. The selected compounds induced also IL-6 and GM-CSF. Their activities were clearly correlated with defined chemical structures as well as with the presence of selenium. We suggest that some of the selected by us compounds, other than ebselen, are interesting as immunostimulants and potential antiviral agents and cytokine inducers active in humans.
Subject(s)
Adjuvants, Immunologic/pharmacology , Organoselenium Compounds/pharmacology , Antiviral Agents/pharmacology , Azoles/pharmacology , Biological Assay , Interferons/biosynthesis , Isoindoles , Leukocytes/drug effects , Organoselenium Compounds/chemistry , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The blood samples taken from 31 HIV+ and AIDS patients were used to study interferon (IFN) and tumor necrosis factor (TNF) responses. The IFN and TNF levels in plasma were determined. In the whole blood assay (whole blood diluted 1:10 with culture medium) Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as cytokine inducers. Blood leukocytes of HIV+ patients produced significantly less IFN-alpha after NDV stimulation than the cells of healthy (HIV-) individuals. On the other hand, the production of IFN-gamma in response to PHA was impaired only in AIDS patients with stage CDC IV and CD4+ cell number < 200/microliters. These patients had also increased IFN levels in plasma. Particularly, the high level of IFN in plasma was frequently detected in patients with progressing AIDS with CD4+ cell number < 50/microliters. This type of IFN was identified as a mixture of acid-labile and acid-stable IFN-alpha. The IFN responses of HIV+ patients may be considered as markers for monitoring progression of AIDS and therapy.
