Influence of systemic inflammatory response syndrome on host resistance against bacterial infections.

Abstract

To determine the relationship between systemic inflammatory response syndrome (SIRS) and host innate immunities against bacterial infections. Controlled animal study. University research laboratory. Male BALB/c mice, 8-10 wks of age. Morbidity and mortality rates of severe SIRS mice were compared with those of mild SIRS mice after infection with Enterococcus faecalis or methicillin-resistant Staphylococcus aureus (MRSA) or exposure to infectious complications induced by cecal ligation and puncture (CLP). In addition, a function of effector cells related to antibacterial innate immunities for these infections was analyzed in these two groups. Furthermore, SCIDbgMN mice (SCIDbg mice depleted of antibacterial effector cells) were reconstituted with effector cells from mild or severe SIRS mice and exposed to various infections. Severe SIRS mice were greatly susceptible to E. faecalis, MRSA, and CLP-induced sepsis. On the other hand, as compared with normal mice, mild SIRS mice were resistant to these infections. All of SCIDbgMN mice inoculated with peritoneal macrophages (PMphi) from severe SIRS mice died after infection with E. faecalis or MRSA, whereas all SCIDbgMN mice inoculated with PMphi from mild SIRS mice survived after the same infection. SCIDbgMN mice that were inoculated with PMphi from normal mice and exposed to E. faecalis, MRSA, or CLP survived at rates of 50%, 50%, or 60%, respectively. PMphi from mild SIRS mice exhibited typical properties for classically activated macrophages (CAMphi), whereas those from severe SIRS mice exhibited typical properties for alternatively activated macrophages (AAMphi). Mphi-associated host antibacterial innate immunities are greatly influenced by SIRS levels. CAMphi, effector cells for the antibacterial innate immunity against E. faecalis, MRSA, and CLP-induced sepsis, are induced in mild SIRS mice. AAMphi with no antibacterial capabilities are generated in mice with severe SIRS. Induction of CAMphi may protect severe SIRS patients against infections.