Bacterial sepsis and chemokines

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 (M1M phi) are major effector cells for host innate immune responses against these infections. However, MIMO are not generated in thermally injured patients whose alternatively activated macrophages (M2M phi) predominate. M2M phi appear in patients early after severe burn injuries. M2M phi inhibit M1M phi generation through the secretion of CCL17 and IL-10. As a modulator of M phi, two different subsets of neutrophils (PMN-I, PMN-II) are described. PMN-I direct the polarization of resident M phi into MIMO through the production of CCL3. M2M phi are induced from resident M phi 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 M1M phi, elimination of CCL2 and/or depletion of M2M phi induced by CCL2.