DOXYCYCLINE REDUCES MORTALITY TO LETHAL ENDOTOXEMIA BY REDUCING NITRIC-OXIDE SYNTHESIS VIA AN INTERLEUKIN-10-INDEPENDENT MECHANISM

It was demonstrated that doxycycline protected BALB/c mice injected in traperitoneally with bacterial lipopolysaccharide (LPS) against lethal septic shock. Doxycycline (at 1.5 mg/kg) exerted its protective effec t by inhibiting nitrate production by an interleukin-10-independent me chanism. Experiments carried out in vitro also indicated that doxycycl ine inhibited NO synthesis by LPS-activated macrophages without induci ng any significant modification in interleukin-10 release. These data suggest that the direct inhibition of nitrate release is the main mech anism of the antiinflammatory activity of doxycycline in septic shock.