Tumor necrosis factor-α and interleukin-1α decrease the adherence of Streptococcus pyogenes to cultured keratinocytes

We hypothesized that the primary epidermal cytokines, tumor necrosis factor (TNF)-alpha and interleukin (TL)-1 alpha, which are produced after skin injury, modulate bacterial adherence and the initiation of group A streptococcal skin infections. Streptococcus pyogenes binds preferentially to highly differentiated keratinocytes in vitro, simulating the superficial human skin infection, impetigo, and providing a model system for testing this hypothesis. Exposure of keratinocytes to 10 ng/mL TNF-alpha for 20 h decreased adherence to undifferentiated and differentiated keratinocytes by 33% and 38%, respectively. Treatment with 1 ng/mL IL-1 alpha decreased adherence to undifferentiated and differentiated keratinocytes by 23% and 18%, respectively. Exposure to both cytokines simultaneously produced an additive 50% reduction in adherence. These data suggest that TNF-alpha and IL-1 alpha may play a role in cutaneous host defense by impeding streptococcal adherence and decreasing its ability to form a nidus of infection in the skin.