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Background  RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic  Staphylococcus aureus  ( S .  aureus ) infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local  S .  aureus  infection (e.g., skin infection) might differ from their effects on a systemic infection.    Aims  The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on  S .  aureus  skin infections in mice.    Method  Abatacept (CTLA4 Ig), etanercept (anti-TNF treatment) or PBS was given to NMRI mice subcutaneously inoculated with  S .  aureus  strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.    Results  Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.    Conclusion  Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for  S .  aureus  skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice