Department of Pharmacology

Manipulation of the cytokine network is a central paradigm for successful immunotherapy. The search for new drugs that would directionally modulate immune system activity has become a permanent challenge for pharmacological research. We investigate possibilities for the pharmacological modulation of immune factors such as cytokines, chemokines, interferons, and nitric oxide. On one side, these factors play critical roles in the defence of organisms against infections and cancer. On the other side, their long-term overproduction is often associated with the etiopathogenesis of many diseases such as asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, etc. Therefore, novel agents that would contribute to both cytokine and anti-cytokine therapies are urgently needed in clinical practice.

Toward this point, the department pays major attention to antiviral acyclic nucleoside phosphonates, to modulators of intracellular calcium (inhibitors of sarco/endoplasmic Ca2+-ATPase, i. e. SERCA inhibitors), natural compounds such as sesquiterpene lactones, and probiotics.

In order to test the cytokine-modulatory activities of both synthetic and natural agents, we have developed a nitric oxide-based, moderate-throughput screening bioassay, allowing for the reliable and inexpensive screening of a drug’s potential to activate cytokine secretion. The data thus obtained in animal cell cultures can be employed to predict the immunomodulatory effects of drugs in cells of human origin.

We have found that many acyclic nucleoside phosphonates activate the production of cytokines interfering with virus replication and chemokines (e. g. RANTES, MIP-1α, MCP-1) that inhibit the penetration of HIV into cells. SERCA inhibitors have been found to be potent inducers of the Th1-type cytokine interferon-gamma (IFN-γ), which plays a crucial role in antiviral activity.

The methods employed to characterize the immunobiological activity of compounds include cell cultures, ELISA, multiplex analysis systems (LUMINEX), RT-PCR, etc. In order to understand the mechanisms of interference of agents with the immune system, the underlying signaling pathways and the expression of transcription factors are analyzed.