Human intravenous immunoglobulin for experimental streptococcal toxic shock: bacterial clearance and modulation of inflammation

Objectives: Polyclonal human intravenous immunoglobulin (IVIG) has been advocated as an adjunct to therapy in severe invasive streptococcal toxic shock because of its ability to neutralize superantigen toxins. The aim of this study was to assess IVIG therapeutic efficacy in an experimental model of streptococcal toxic shock. Methods: To confirm the in vitro activity of IVIG against the Streptococcus pyogenes strain used in the study, IVIG was tested for superantigen neutralizing and bacterial opsonizing activity prior to in vivo studies. To evaluate the in vivo effects of IVIG in terms of microbiological outcome and disease severity in a superantigen-sensitive transgenic model of streptococcal shock, HLA-DQ transgenic mice were treated with IVIG either at the time of infection or after infection with S. pyogenes. Antibiotics were included in some studies. Results: The IVIG preparation neutralized superantigenicity of S. pyogenesin vitro and enhanced bacterial killing in a whole blood assay. When given to mice at the time of S. pyogenes infection, IVIG neutralized circulating superantigens and reduced systemic inflammatory response. Remarkably, IVIG-enhanced systemic clearance of bacteria and enhanced neutrophil infiltrate into the infected tissues. However,when used in combination with penicillin and clindamycin in a delayed treatment setting, IVIG did not confer additional therapeutic benefit, in terms of inflammatory response, bacterial clearance or survival. Conclusions: IVIG monotherapy can confer benefit in experimental streptococcal shock, but extension of these findings to the clinical situation will require further evaluation.