The immune response to severe bacterial infections: consequences for therapy

Abstract

The immune response to a bacterial stimulus starts when pathogen-associated molecular patterns of the bacterial pathogens activate pattern recognition receptors of the innate immune system. This leads to production of proinflammatory and anti-inflammatory mediators aiming to contain infection and drive the clinical signs of sepsis. When sepsis and signs of failing organs are apparent, proinflammatory phenomena have ceased; a hypoinflammatory phase predominates, characterized by anergy of monocytes and apoptosis of T lymphocytes. The above sequence of events seems to differ from one patient to the next. The majority of therapies targeting the immune responses have failed to provide clinical benefit. Immunostimulation with IFN-γ and leukocyte growth factors, hemoperfusion with polymyxin B-embedded fiber column, and macrolides remain the most promising immunomodulators in clinical practice.

Keywords::

• apoptosis
• bacterial infections
• cytokines
• immunostimulation
• macrolides
• monocytes
• sepsis

Financial & competing interests disclosure

EJ Giamarellos-Bourboulis has received three unrestricted educational grants by ABBOTT Hellas SA; he has also received unrestricted educational grants by Janssen-Cilag Hellas SA, by Sanofi-Aventis Hellas SA and by Wyeth Hellas SA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.