Influence of fumaric acid derivates on T lymphocytes in the murine model of HSV-1 keratitis
I. Weinmann1, A. Schmitz1, D. Bauer1, S. Wassmuth, A. Heiligenhaus1,2
Purpose: It has been previously shown that fumaric acid derivates are able to modulate cytokine response of T-lymphocytes in psoriasis vulgaris most probably by selective stimulation of T-helper-2 (Th2) cytokines. In HSV-1-stromal keratitis (HSK), CD4+ T-lymphocytes are important mediators. Predominantly T-helper-1 (Th1) cytokines participate in the development of HSK while the systemic administration of Th2-cytokines Interleukin-4 und 10 (IL-4, IL-10) improved the disease. This study was performed to determine wether fumaric acid derivates i.e. monomethylfumarate (MMF) and Calciumdimethylfumarate (CaMF) are able to increase Th2-cytokine expression even during development of HSK.
Methods: Fourteen days after infection with HSV-1 a mixed lymphocyte suspension was prepared from spleen and regional lymphnodes. Cells were cocultivated with MMF, CaMF and further more with UV-inactivated HSV-1. Stimulation with Concavalin A served as control. After incubation for 24h supernants were harvested. The presence of Th1 and Th2 cytokines IL-2, IFN-g , IL-4 and IL-10 was analyzed by an indirecte ELISA examination and influence of MMF and CaMF on proliferation of stimulated and unstimulated lymphocytes was measured by a proliferationsassay.
Results: MMF and CaMF was found to increase the IL-4 and IL-10 production in splenic or regional lymph node cells. The production of IL-2 or IFN-g was not affected. There was no influence of MMF and CaMF on HSV antigen specific lymphocyte proliferation.
Conclusions: Fumaric acid derivates are able to induce the Th2 cytokine production without affecting the Th1 cytokine secretion in a murine model of HSK. Studies are in progress to investigate whether fumaric acid derivates may be helpful to improve the course of stromal HSV-1 keratitis.
1Department of Ophthalmology, University, Essen, Germany