Novel Molecular Targets in the Search for Anti-Inflammatory Agents

In the chronic state of inflammatory diseases, cellular signaling networks aimed at combating invading pathogens are often constitutively active and transmit their signals even in the absence of inflammatory agents. Thus, many anti-inflammatory drugs interfere with these dys- and hyperactivated cellular signaling networks or transcription factors. As many signaling molecules fulfill important and essential functions in normal cell physiology, their systemic and long-term inhibition may lead to severe side effects including an impaired immune response. To circumvent these pitfalls, two possibilities are proposed and discussed here: (I) Since many inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease are restricted to certain cell types or tissues, a new generation of anti-inflammatory drugs would target enzymes that are only operational in these affected tissues. (II) As some signaling pathways affect solely a small subset of inflammatory target genes, their inhibition bears the potential of limiting potential side effects.