Anti- TWEAK monoclonal antibodies reduce vascular damage and leucocyte infiltration in a mouse model of cutaneous reverse passive Arthus reaction.

Background Tumour necrosis factor ( TNF)-like weak inducer of apoptosis ( TWEAK) is a pro-inflammatory cytokine, which is closely associated with the pathogenesis of various types of cutaneous vasculitis ( CV). Aim To investigate the therapeutic effects of an anti- TWEAK monoclonal antibody ( mAb) in a mouse model of cutaneous reverse passive Arthus ( RPA) reaction. Methods Cutaneous RPA reaction was induced in BALB/c mice by intradermal injection of anti-ovalbumin IgG into the left ear followed immediately by intravenous injection of chicken ovalbumin. After treatment, haemorrhagic lesions in the mouse skin were scored semiquantitatively. The amount of extravasated fluorescein isothiocyanate ( FITC)-labelled bovine serum albumin ( BSA) in the ears was detected spectrophotometrically. Expression of myeloperoxidase ( MPO) was detected by immunohistochemical staining, while mRNA expression of TNF-α and interleukin ( IL)-6 in lesional skin was detected by real-time quantitative (q) PCR. Results Our results indicated that anti- TWEAK mAb significantly attenuated the clinical and histopathological changes in immune complex ( IC)-induced mice, and also reduced the semiquantitative haemorrhage score, FITC-labelled BSA extravasation and MPO activity. Real-time qPCR showed that anti- TWEAK mAb significantly inhibited mRNA expression of TNF-α and IL-6 in lesional skin from IC-induced mice. Conclusion These data suggest that anti- TWEAK mAb can block vascular damage and leucocyte infiltration in IC-induced mice. TWEAK might be a candidate immunotherapeutic medicine for suppression of IC-induced CV. [ABSTRACT FROM AUTHOR]