Anti-inflammatory Effects of Variola Virus TNF Decoy Receptor in an Experimental Model of Contact Dermatitis

Abstract

Background: Large DNA poxviruses encode a diverse family of secreted proteins that modulate host inflammatory and antiviral responses, in particular by inhibiting one of the key players of the mammalian immune system, the tumor necrosis factor (TNF).

Methods: We investigated the effects of a recombinant variola (smallpox) virus TNF-decoy receptor (VARV-CrmB) in a murine model of contact dermatitis. Our results demonstrate that the VARV-CrmB protein significantly reduces the 2,4-dinitrochlorbenzene (DNCB)-induced migration of skin leukocytes during the sensitization phase and suppresses ear oedema during the elicitation phase of the contact reaction.

Results: Studies focusing on the bone marrow hematopoiesis in the contact dermatitis model revealed that the epicutaneous co-application of DNCB and VARV-CrmB protein normalized the DNCBinduced effects to control levels.

Conclusion: As an effective TNF antagonist, the VARV-CrmB protein might be conceived as a beneficial candidate for further research and development of therapeutic approaches in the field of the inflammatory skin diseases.

Keywords: Bone marrow; TNFdecoy receptor; cell migration; contact dermatitis; hematopoiesis; human TNF (hTNF); murine TNF (muTNF); variola virus..