Therapeutic strategies in pneumonia: going beyond antibiotics

Abstract

Dysregulation of the innate immune system drives lung injury and its systemic sequelae due to breakdown of vascular barrier function, harmful hyperinflammation and microcirculatory failure, which contribute to the unfavourable outcome of patients with severe pneumonia. A variety of promising therapeutic targets have been identified and numerous innovative therapeutic approaches demonstrated to improve lung injury in experimental preclinical studies. However, at present specific preventive or curative strategies for the treatment of lung failure in pneumonia in addition to antibiotics are still missing. The aim of this mini-review is to give a short overview of some, but not all, adjuvant therapeutic strategies for pneumonia and its most important complications, sepsis and acute respiratory distress syndrome, and briefly discuss future perspectives.

FIGURE 1

Time course of inflammation, tissue damage and resolution of pneumonia: potential adjuvant therapies. Subsequent to ligand binding pathogen recognition receptors initiate the host inflammatory response, including cytokine production, recruitment of leukocytes and activation of the complement system, thereby leading to elimination of the pathogen and infected cells. However, immune overactivation may lead to tissue damage and barrier failure. From the beginning of the inflammatory response, pulmonary repair and resolution processes are initiated to balance damage and healing of the tissue, ideally resulting in restoration of the original condition (restitutio ad integrum). Potential adjuvant therapies target different processes during pneumonia, thereby potentially exerting beneficial functions in addition to antibiotic treatment. DAMPs: danger-associated molecular patterns; PRRs: pattern recognition receptors; GM-CSF: granulocyte-macrophage colony-stimulating factor.