title: Bacterial sepsis and chemokines.
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 (M1Mphi) are major effector cells for host innate immune responses against these infections. However, M1Mphi are not generated in thermally injured patients whose alternatively activated macrophages (M2Mphi) predominate. M2Mphi appear in patients early after severe burn injuries. M2Mphi inhibit M1Mphi generation through the secretion of CCL17 and IL-10. As a modulator of Mphi, two different subsets of neutrophils (PMN-I, PMN-II) are described. PMN-I direct the polarization of resident Mphi into M1Mphi through the production of CCL3. M2Mphi are induced from resident Mphi 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 M1Mphi, elimination of CCL2 and/or depletion of M2Mphi induced by CCL2.
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77555-0435, USA.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.forename: Tokuichiro
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002056:Burns / Q000150:complications / Q000382:microbiology; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D007167:Immunotherapy; D018805:Sepsis / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology* / Q000628:therapy
chemical_list: D018925:Chemokines