MODELING TH1-TH2 REGULATION, ALLERGY, AND HYPOSENSITIZATION

摘要

Modeling Thl-Th2 regulation needs of course simplification of a very complex scheme. Our intention was to explain hyposensitization therapy as a dynamic effect of Thl-Th2 regulation. The dynamic behaviour of the model and experimental results support this hypothesis. The desensitized state is a temporary state, in vivo and in the developed model. Model simulations show, for example, that even one missed allergen injection during therapy or one too high allergen dose may endanger the success of hyposensitization. In case of a missed allergen injection it may be helpful to decrease the dose of the next allergen injection. Other simulations show that the application of cytokines, which meets however difficult problems in practice, seems to be a conceivable way in therapy. The mathematical model offers the possibility to test variations in the schedule of administration, e.g. changing doses and intervals between injections, which may help in practice to optimize therapies. Thl-Th2 regulation, especially the switch from the dominance of one T-cell subset to another, has a special role not only in allergy. Altered profiles of Thl-Th2 type cytokine production may be associated also with other diseases in humans such as candidiasis, AIDS, Leishmania and autoimmune diseases. Antigen administration could provoke a switch in the T-cell dominance in these diseases, too. For a very recent survey of current research the reader is referred to Abbas et al. (1997) and to Romagnani and collaborators (1997). We are confident that mathematical models of T-cell regulation could provide assistance in understanding these diseases and may help to develop and to optimize therapeutic strategies.