Abstract
Bacterial sepsis causes a high mortality rate when it occurs in patients with compromised host defenses. Severely burned patients, typical immunocompromised hosts, are extremely susceptible to infections from various pathogens, and a local wound infection frequently escalates into sepsis. In these patients, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa are familiar pathogens that cause opportunistic infections. Also, polymicrobial sepsis frequently occurs in these patients. In this review, therefore, the roles of chemokines in thermally injured patients infected with these 3 pathogens and polymicrobial sepsis will be discussed. These infections in thermally injured patients may be controlled immunologically, because immunocompetent hosts are resistant to infections with these pathogens. Classically activated macrophages (M1Mφ) are major effector cells for host innate immune responses against these infections. However, M1Mφ are not generated in thermally injured patients whose alternatively activated macrophages (M2Mφ) predominate. M2Mφ appear in patients early after severe bum injuries. M2Mφ inhibit M1Mφ generation through the secretion of CCL17 and IL-10. As a modulator of Mφ, two different subsets of neutrophils (PMN-I, PMN-II) are described. PMN-I direct the polarization of resident Mφ into M1Mφ through the production of CCL3. M2Mφ are induced from resident Mφ by CCL2 released from PMN-II. Therefore, as an inhibitor of CCL2, glycyrrhizin protects individuals infected with S. aureus. Sepsis stemming from P. aeruginosa wound infection is also influenced by CCL2 released from immature myeloid cells. A large number of immature myeloid cells appear in association with burn injuries. Host resistance to S. aureus, E. faecalis, P. aeruginosa or polymicrobial infections may be improved in thermally injured patients through the induction of M1Mφ, elimination of CCL2 and/or depletion of M2Mφ induced by CCL2.
Original language | English (US) |
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Pages (from-to) | 119-134 |
Number of pages | 16 |
Journal | Current Drug Targets |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2006 |
Externally published | Yes |
Keywords
- Burn injury
- CCL2
- CCL3
- M1 macrophages
- M2 macrophages
- Opportunistic infections
- PMN-I
- PMN-II
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Clinical Biochemistry