supernatants from staphylococcus aureus grown in the presence of b-lactam antibiotics induce release of nitric oxide from mouse macrophages

introduction: septic shock is now recognized to be associated with multiple critical organ failure, usually attributable to the uncontrolled release of multiple pro-inflammatory cytokines such as tnf, inf, il-6, il-1, and no (nitric oxide). no is one of the most important proinflammatory mediators in sepsis and septic shock. it is a potent vasodilator, and appears to be responsible for hypotension in sepsis patients. on the other hands, antibiotic action on the microbes in the host can result in release of bacterial components that will trigger a host proinflammatory response. in the present study we examined the effects of a number of -lactam antibiotics (cloxacillin, ampicillin or ceftazidim) on the release of bacterial products from staphylococcus aureus and their effect on no production by mouse macrophages. material and methods: mics and mbcs of antibiotics for s. aureus were determined by standard macrodilution method. s. aureus was incubated in absence (control) or presence of mbc concentrations of three -lactam antibiotics. supernatants of the cultures obtained by filtration were added to plastic adherent peritoneal murine macrophages. after 24 hrs incubation, macrophage supernatants were tested for the presence of nitric oxide by griess reagents. results: supernatants from bacteria incubated with -lactam antibiotics induced significantly higher nitric oxide levels than those obtained from bacteria incubated with culture medium only (no antibiotics). the effects of the three â-lactam antibiotics to generate nitric oxide release from s. aureus were similar. conclusions: the results indicate that release of bacterial components during â-lactam antibiotic treatment of s. aureus, can play an important role in proinflammatory response.