Inflammation – A New Therapeutic Target in Pneumonia

Abstract

Inflammation is a hallmark of pneumonia. Therefore, managing inflammation is an attractive adjunct to targeted antibiotic therapy, mainly in severe pneumonia. Recent investigations indicate that glucocorticoids given in physiological doses (from 10-fold to 100-fold less than doses administered in the past) could be of benefit. We could also manage inflammation by administering or influencing cytokines. A major concern is that drugs designed to target a single cytokine or receptor could prove ineffective due to the redundancy of signaling pathways involved. This may require selection of drugs with broad activity or the targeting of molecules common to inflammatory signaling pathways. Drugs affecting multiple molecules or key inflammatory pathway intermediates could be more effective, but their use will need to be weighed against the risk of impairing innate immunity. Indirect approaches to manage inflammation, such as neutralizing cytotoxic substances in the lung (e.g., inhibiting, neutralizing and eliminating endotoxin), could be used in combination with other approaches. Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy, although intense clinical research with immunotherapy has not yet yielded a successful treatment adjunct. We believe that compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.

Stopping Bacterial Adhesion: A Novel Approach to Treating Infections

“…In order to address the problems of resistance to existing antimicrobial agents [1, 2], the limited efficacy of existing antibiotics in the treatment of bacterial infections that form biofilms [3, 4] and the apparent increase in hospital-acquired infections and infections of the lower respiratory tract [5], novel approaches are required to develop effective antimicrobials. Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a good theoretical target for new therapies.…”

Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia

“…Although the number of cytokines identified in the immunopathogenesis of CAP has increased considerably over the years, studies remain focused on well-known cytokines of the innate immune response, including interleukin (IL)-6, IL-10, IL-8, IL-1b and tumour necrosis factor (TNF)-a. IL-17A and IL-22, which belong to the novel T-helper (Th) 17 subset, have also been implicated in CAP [2,3]. Furthermore, interferon (IFN)-c is an important cytokine in both innate and adaptive immunity to respiratory pathogens [16], and IL-4 might be important in the immune response against Mycoplasma pneumonia [17]. Further characterisation of local and systemic cytokine responses in CAP patients may increase our understanding of the host defence, with the goal of providing prognostic tools for clinicians or identifying potential therapeutic targets.…”

Immunogenetics of Severe Respiratory Infections: Models for the Development of New Therapeutic Strategies

“…Disease association genetic studies and the ensuing molecular structure/function studies are likely to shed light upon disease mechanisms and provide leads indicating which factors of the innate arm of immunity [76, 77] might be used as template for the design of agonist and antagonist molecules, anti-bacterial and anti-inflammatory agents that might be relevant to the treatment of severe pneumonia and sepsis [78, 79]. …”