Peptides and polypeptides as modulators of the immune response: thymopentin--an example with unknown mode of action.

Peptides and polypeptides play a critical role in the immune system and are therefore predestined as a source for new approaches in immunotherapy. For example, antigenic peptides which can trigger a specific immunological response have been successfully used for vaccination. In contrast, cytokines have to be considered as rather non-specific immunomodulators. In addition, certain peptides with unknown mode of action have shown promising immunomodulating properties. An example is the pentapeptide thymopentin (TP5), which represents the active sequence of the originally described thymopoietin (TP). TP was recently identified as a fragment of the thymopoietins (TMPOs), a family of nuclear proteins. In vitro assays showed that TP5 affects the function of T cells and monocytes measured by enhanced cGMP level and the triggering of cellular signalling, respectively. In vivo studies demonstrated the capability of TP5 to improve an imbalanced immune system. TP5 exhibited important clinical features and further investigations on its mode of action are necessary to rationally create TP5 peptide analogs or peptidomimetics.