Staphylococcal enterotoxin C1-induced pyrogenic cytokine production in human peripheral blood mononuclear cells is mediated by NADPH oxidase and nuclear factor-kappa B

The staphylococcal enterotoxins produced by Staphylococcus aureus are associated with pyrogenic response in humans and primates. This study investigates the role of NADPH oxidase and nuclear factor-kappa B (NF-kappaB) on enterotoxin staphylococcal enterotoxin C1 (SEC1)-induced pyrogenic cytokine production in human peripheral blood mononuclear cells (PBMC). The results indicate that the febrile response to the supernatant fluids of SEC1-stimulated PBMC in rabbits was in parallel with the levels of interleukin-1beta and interleukin-6 in the supernatants. The release of interleukin-1beta and interleukin-6, nuclear translocation of NF-kappaB and its DNA binding activity in the SEC1-stimulated PBMC were time-dependent and were completely eliminated by pyrrolidine dithiocarbamate or SN-50 (NF-kappaB inhibitors). The release of reactive oxygen species in the supernatants and translocation of the NADPH oxidase p47(phox) subunit to the plasma membrane of SEC1-stimulated PBMC were time-dependent. Administration of apocynin (NADPH oxidase inhibitor) attenuated the febrile response to the supernatants in rabbits and decreased the translocation of NADPH oxidase p47(phox) subunit and NF-kappaB activity in the SEC1-stimulated PBMC, and suppressed reactive oxygen species and pyrogenic cytokine production in the supernatants. Taken together, SEC1 may act through an NADPH oxidase mechanism to release reactive oxygen species, which activate NF-kappaB in PBMC to stimulate the synthesis of pyrogenic cytokines that trigger a fever response in rabbits.