Oral warfarin affects some aspects of systemic immunomodulation with topical dinitrochlorobenzene (DNCB) in rats

Abstract

Purpose: The efficacy of topical dinitrochlorobenzene (DNCB) in the treatment of some skin dermatoses is based both on local and systemic effects. It is not known, however, whether it can be applied to patients receiving some other therapy associated with systemic immunomodulation. The aim of the present paper using a rat model was to examine whether oral warfarin (WF) intake, as shown by others and by us, had an immunomodulatory potential to interfere with effects of topical DNCB as systemic immunotherapy.

Materials and methods: Rats received 3.5 mg/l of WF sodium in drinking water for 30 days and were thereafter skin-sensitized with 0.4% DNCB. Changes in the oxidative activity (myeloperoxidase/MPO, reduction of nitroblue tetrazolium/NBT and nitric oxide/NO production) as well as tumor necrosis factor (TNF) production by peripheral blood polymorphonuclear cells (PMN) were measured and compared with PMN from sensitized unexposed to WF rats.

Results: WF intake enhanced some aspects of PMN activity (intracellular MPO activity and unstimulated NO production) as well as their responsiveness to exogenous stimulation (NBT reduction and TNF production from sensitized animals). However, WF also decreased PMN responsiveness of NO production to stimulation. WF affected NO and TNF production solely by PMN, as no effect on these activities of peripheral blood mononuclear cells was seen.

Conclusion: Having in mind that polymorphonuclear leukocytes are the most abundant cell type in peripheral blood in humans, increase of basic aspects of PMN activity described in the present paper might be relevant for consideration of using WF as therapeutic modality in patients topically treated with DNCB.

Keywords:

• Oral warfarin intake
• peripheral blood mononuclear cells
• peripheral blood polymorphonuclear cells
• rats
• topical dinitrochlorobenzene

Acknowledgements

This study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia [Grant #173039]. The authors would like to thank Jelena Demenesku for her assistance in some of the experiments.

Declaration of interest

The authors declare that there are no conflicts of interest in this study. The authors alone are responsible for the content of this manuscript.