| Description |
Group A streptococcus (GAS) is a severe, and potentially fatal, cause of postpartum infection. Bacterial virulence factors influence pathogenesis but do not effectively predict disease susceptibility or severity. Our objective was to determine if an altered maternal innate immune response is associated with puerperal group A streptococcus sepsis. We stimulated peripheral blood mononuclear cells from patients with previous postpartum puerperal GAS infection and compared cytokine/inflammatory marker production to age, parity, and racially matched controls. Concentrations of 13 cytokines/inflammatory markers including IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, IL-2r, and soluble CD40 ligand were measured in mononuclear cell cultures from patients and controls in response to heat-killed emm1 and emm28 group A streptococci, the M-serotypes most closely associated with puerperal morbidity. Samples from ten controls, ten severe cases, and six mild cases were analyzed. In response to stimulation, IL-1β, IL-6, IL-2r, IL-10, IL-13, and CD40L cytokine production were significantly increased in severe and mild cases combined, compared to control samples (IL-1β mean response 1143.3 vs. 502.3 pg/ml, p<0.01; IL-13 mean response 8.8 pg/ml vs. 5.7 pg/ml pg/ml, p<0.05; and CD40L mean response 131.7 vs. 69.2 pg/ml, <0.0001). IL-4 concentrations in patients were not statistically different from controls. When stratified, severe cases also had a significant response when compared to mild cases. IL-5, IL-2, and IL-12 stratified cases also showed a more robust response in the severe groups when compared to mild groups, but were not statistically significant. Puerperal group A streptococcal sepsis is associated with altered maternal innate inflammatory immune responses. The increased production of inflammatory cytokines many contribute to susceptibility and severity of puerperal group A streptococcal disease. |
