What is the pathophysiology of the septic host upon admission?

Giamarellos‐Bourboulis, Evangelos J.

doi:10.1016/j.ijantimicag.2010.11.003

Cited by 33 publications

(36 citation statements)

References 21 publications

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“…(ii) Subpopulations of lymphocytes were not studied. However, daily measurements of the ratio of circulating IL-10/TNF-␣ are proposed to represent an indirect index of the existing balance between Th1 and Th2 cell responses (2). (iii) The intracellular concentrations of clarithromycin in isolated monocytes and neutrophils were not measured.…”

Section: Figmentioning

confidence: 99%

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Spyridaki

Rosario

Antonopoulou

et al. 2012

Antimicrob Agents Chemother

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dOne recent, double-blind, randomized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia (VAP) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions (MODS). The present study focused on the effect of clarithromycin on markers of inflammation in these patients. Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment. The concentrations of circulating markers were measured. Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation. The ratio of serum interleukin-10 (IL-10) to serum tumor necrosis factor alpha (TNF-␣) was decreased in the clarithromycin group compared with the results in the placebo group. Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group. On the same day, the expression of CD86 was increased and the ratio of soluble CD40 ligand (sCD40L) to CD86 in serum was unchanged. The release of TNF-␣, IL-6, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group. The expression of TREM-1 on monocytes was also increased in the former group. These effects were pronounced in patients with septic shock and MODS. These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis; this was accompanied by more efficient antigen presentation and increased apoptosis. These effects render new perspectives for the immunotherapy of sepsis.

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Section: Figmentioning

confidence: 99%

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Spyridaki

Rosario

Antonopoulou

et al. 2012

Antimicrob Agents Chemother

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“…Unfortunately, P. aeruginosa has the ability to develop resistance to multiple classes of antibacterial-effective drugs, so that treatment of an infection has become a serious clinical problem (21). Not uncommonly, infections with Gram-negative bacteria (including P. aeruginosa) resulted in systemic inflammatory response syndrome, sepsis, or septic shock (16). These inflammatory diseases are life-threatening conditions that require comprehensive treatment in intensive care units.…”

Section: Discussionmentioning

confidence: 99%

“…Systemic bacterial infections and bacterial sepsis are dangerous and potentially lethal disease conditions that occur in response to bacteria or other microbial pathogens (14)(15)(16). Pseudomonas aeruginosa is an opportunistic pathogen of immunocompromised humans which typically infects the pulmonary tract, causing bacterial pneumonia (17).…”

mentioning

confidence: 99%

Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes

et al. 2016

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Infections with Pseudomonas aeruginosa may cause many different diseases. The spectrum of such infections in general includes inflammation and bacterial sepsis. Hospital-acquired pneumonia, naturally resistant to a wide range of antibiotics, is associated with a particularly high mortality rate in mechanically ventilated patients. The pathogenesis of P. aeruginosa is complex and mediated by several virulence factors, as well as cell-associated factors. We have previously demonstrated that stimulation with different bacteria triggers the cytokine response of thymocytes. In this study, we investigated the effect of P. aeruginosa and its different components on the cytokine production of immature and mature immune cells. We found that the induced cytokine pattern in the thymus and the spleen after infections with P. aeruginosa is primarily mediated by lipopolysaccharide (LPS) of the outer cell membrane, but other components of the bacterium can influence the cytokine secretion as well. Stimulation with heatkilled P. aeruginosa and LPS does not influence the amount of cytokine-producing CD4 ؉ T cells but instead suppresses the emergence of Th17 cells. However, stimulation with P. aeruginosa or its components triggers the interleukin-17 (IL-17) response both in thymocytes and in splenocytes. We conclude that infections with P. aeruginosa affect the cytokine secretion of immature and mature cells and that IL-17 and Th17 cells play only a minor role in the development of pathological systemic inflammatory disease conditions during P. aeruginosa infections. Therefore, other inflammatory immune responses must be responsible for septic reactions of the host. Interleukin-17 (IL-17) is a potent inflammatory cytokine, which was initially reported to be produced mainly by activated memory T cells, also called T helper (Th) 17 cells (1). In addition to induced IL-17-producing T cells, which are primed in the immune periphery during the induction of an antigen-specific T cell response, these IL-17-producing cells are also present in the thymuses of naive wild-type mice (2, 3). In most mice, IL-17-producing thymocytes represent a subpopulation of CD4 ϩ T cells which are able to react immediately on environmental stimuli without further priming phase (2-5). Furthermore, innate immune cells can also produce IL-17 in response to early immune mechanisms (6). Intrinsically, IL-17-producing cells, also referred to as the sentinels of the immune system, play a critical role in several fields of innate and adaptive immunity, including immunity against microbial infections and tumors (6-9). Dysregulated IL-17 production can result in uncontrolled proinflammatory cytokine production and chronic inflammation, promoting tissue damage and leading to autoimmune diseases (10-12). The most commonly used animal model for the human inflammatory demyelinating disease multiple sclerosis is experimental autoimmune encephalomyelitis (EAE) (13).Systemic bacterial infections and bacterial sepsis are dangerous and potentially lethal disease conditions t...

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“…Patients with sepsis and the background of neutrophil sequestration can often develop complications in tissues, such as ARDS, and excessive activation of neutrophils is associated with lung destruction (Kumar V. et al, 2010, Giamarellos-Bourboulis E.J. et al, 2010.…”

Section: Functional Activity Of Leukocytesmentioning

confidence: 99%

“…A part of this condition is the disorder in phagocytic function of neutrophils, which to a high extent determines anti-infectious defense (Volk H.D. et al, 1999, Alves-Filho J.C. et al, 2010, Giamarellos-Bourboulis EJ et al, 2010.…”

Section: Functional Activity Of Leukocytesmentioning

confidence: 99%

Immunological Pathogenesis of Septic Reactions and Elimination of Triggers and Mediators of Inflammation

Shubina¹,

Anisimova²,

Громова³

et al. 2012

Insight and Control of Infectious Disease in Global Scenario

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What is the pathophysiology of the septic host upon admission?

Cited by 33 publications

References 21 publications

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes

Immunological Pathogenesis of Septic Reactions and Elimination of Triggers and Mediators of Inflammation

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