Phagocyte function and cytokine production in community acquired pneumonia.

Moussa, K; Michie, H J; Cree, Ian A.; McCafferty, Ann C.; Winter, John; Dhillon, D P; Stephens, Sue; Brown, Richard A.

doi:10.1136/thx.49.2.107

Cited by 68 publications

(50 citation statements)

References 19 publications

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“…The correlation between sepsis and increased sIL-2R has been previously described in non-transplant patients. 20,21 Approximately one half of our patients had documented bacterial infections and in this group significantly higher sIL-2R levels were noted during week 4. In addition to bacterial infections one should note that viral pathogens, such as cytomegalovirus, can also cause an increase in sIL-2R.…”

Section: Discussionmentioning

confidence: 79%

Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogeneic bone marrow transplantation

Foley

Couban

Walker

et al. 1998

Bone Marrow Transplant

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Summary:Acute graft-versus-host disease (GVHD) is effected by donor T lymphocytes which have been stimulated by host antigens. Activated donor T lymphocytes express interleukin-2 receptor (IL-2R), which is comprised of three subunits (␣, ␤, ␥). During activation, the ␣ IL-2R subunit (CD25) is shed from the receptor complex and can be measured in the circulation. Soluble IL-2R␣ (sIL-2R) levels are increased in states of immune activation including GVHD, and could theoretically be used as a guide to therapy. Since IL-2R␣ expression is an early marker of T cell activation, we investigated: (1) if an increase in sIL-2R is specific for acute GVHD; and (2) if serial sIL-2R levels can identify patients with early GVHD, prior to the onset of clinical tissue damage (effector function). Weekly sIL-2R levels were monitored in 36 patients undergoing matched related (n ‫؍‬ 23) or matched unrelated (n ‫؍‬ 13) allogeneic bone marrow transplantation (BMT). There was no significant difference in sIL-2R levels between matched related and matched unrelated recipients. Patients with acute GVHD (n ‫؍‬ 19, 53%) demonstrated higher sIL-2R levels, than those without during weeks 2 and 3 post-BMT (P ‫؍‬ 0.02 and 0.04, Mann-Whitney U test, twotailed). In patients with acute GVHD, the rise in sIL-2R preceded the clinical signs of GVHD (16/19 patients). However, patients with sepsis demonstrated a trend towards higher sIL-2R levels at week 1 and significantly greater levels by week 4 (P = 0.02). Furthermore, patients with veno-occlusive disease (VOD) (25%) also had significantly higher sIL-2R levels at week 2 (P ‫؍‬ 0.03). We conclude that although sIL-2R levels increase in patients with acute GVHD, similar increases are seen in patients with VOD and/or sepsis and therefore, as a single biochemical marker, we find that serial measurements of sIL-2R lacks sufficient specificity to guide GVHD therapy.

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Section: Discussionmentioning

confidence: 79%

Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogeneic bone marrow transplantation

Foley

Couban

Walker

et al. 1998

Bone Marrow Transplant

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“…However, other studies have documented the presence of systemic inflammation in patients with more severe BP and found that serum IL-6 and TNF-␣ levels correlated with the severity of pneumonia and mortality (3,22,25,27). Thus, in one study of consecutive patients with BP, serum IL-6 and TNF-␣ were present only in 23 and 41% of patients, respectively, whereas in another study of patients with severe pneumonia requiring mechanical ventilation, IL-6 and TNF-␣ were detected in all patients (3,23). In the present study, a cytokine pattern similar to that found in patients with severe pneumonia was observed in HIV-infected patients with BP: 99 and 100% of patients had detectable plasma IL-6 and TNF-␣ levels, respectively, However, our patients with BP did not show clinical criteria of severity: only 5 out of 118 (4%) required admission to the intensive care unit, and 4 (3%) required mechanical ventilation, with 3% mortality.…”

Section: Discussionmentioning

confidence: 99%

“…The local and systemic inflammatory response in BP, with special emphasis on the patterns of cytokines and levels of CRP, has been studied in recent years in the immunocompetent population (20,22,23,27). An increase in proinflammatory cytokines, such as IL-1␤, IL-6, and TNF-␣, as well as acute-phase proteins, such as CRP, has been described in BP (20,27).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

Benito

Moreno

Filella³

et al. 2004

Clin Vaccine Immunol

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We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1␤ (IL-1␤), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-␣) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P ‫؍‬ 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P ‫؍‬ 0.045); and TNF-␣, 46.4, 44, and 75 pg/ml, respectively (P ‫؍‬ 0.029). There were no significant differences in levels of IL-1␤, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-␣ levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).

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“…Pulmonary IL-6 secretion has been observed in the lungs of patients with pneumonia as well as in murine models of pneumococcal pneumonia (3,5,15). It plays a major role in the induction of the cytokine network in lungs and the acute-phase protein response, so that IL-6 genedeficient mice show an impaired defense against pneumococcal pneumonia (23).…”

Section: Discussionmentioning

confidence: 99%

Kinetic Study of the Inflammatory Response in Streptococcus pneumoniae Experimental Pneumonia Treated with the Ketolide HMR 3004

Duong

Simard

Bergeron

et al. 2001

Antimicrob Agents Chemother

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Patients still die from Streptococcus pneumoniae pneumonia after initiation of antibiotic therapy, when tissues are sterile and the pneumonia is clearing. There is growing evidence that overwhelming inflammation resulting from toxin release contributes to tissue injury, shock, and death. Monitoring host response may help us understand the consequences of antibiotic therapy for the inflammatory processes that occur in bacterial pneumonia. HMR 3004 is a ketolide that displays excellent in vitro activity against S. pneumoniae. In the present experiment, we investigated the chronology of inflammatory events that occur during pneumococcal pneumonia in mice treated with HMR 3004. Infection of mice with 10 7 CFU of living S. pneumoniae resulted in 100% mortality within 5 days. HMR 3004 given at 12.5 mg/kg of body weight/dose twice daily from 48 h postinfection achieved complete bacterial clearance from lungs and blood within 36 h and ensured survival of mice. Recruitment of neutrophils and monocytes from blood to lungs was significantly reduced, and nitric oxide release was totally prevented. Interleukin-6 secretion in lungs and blood became rapidly undetectable after initiation of therapy. Histological examination of lung tissue showed protection of interstitium against edema. By controlling bacterial invasion, HMR 3004 led to rapid and profound modifications of the host response in lungs, which may protect mice from deleterious inflammatory reactions.Streptococcal pneumonia is the most common cause of community-acquired bacterial pneumonia. The worldwide increase in the resistance of Streptococcus pneumoniae to penicillin G and other antimicrobials has dramatically complicated the management of pneumococcal infections (2,16,17,25). HMR 3004 belongs to the ketolide family, which represents a class of 14-membered ring macrolide agents that are characterized by a keto group at position 3 of the macrolactone ring, which replaces the L-cladinose moiety of other members of the macrolide group. Studies with HMR 3004 have indicated that ketolides offer a potential alternative for treating penicillin-and erythromycin-resistant S. pneumoniae strains (1,7,12,20,21). HMR 3004 activity was tested against erythromycin-resistant pneumococci in murine pneumonia models: the bactericidal activity of the drug in the lungs was associated with good pulmonary diffusion and a slightly prolonged half-life compared to those of typical 14-membered ring macrolides (P. Rajagopalan-Levasseur, E. Vallée, C. Agouridas, J. F. Chantot, and J. J. Pocidalo, Abstr. 35th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F173, 1995).Pulmonary phagocytic cell recruitment and inflammatory mediator release also play a pivotal role in the effective killing of respiratory pathogens. However, there is increasing evidence indicating that during acute bacterial pneumonia the combination of bacterial virulence factors and excessive inflammatory reactions from the host together contribute to induce severe lung injury, shock, and death (reviewed in references 3...

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Phagocyte function and cytokine production in community acquired pneumonia.

Cited by 68 publications

References 19 publications

Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogeneic bone marrow transplantation

Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogeneic bone marrow transplantation

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

Kinetic Study of the Inflammatory Response in Streptococcus pneumoniae Experimental Pneumonia Treated with the Ketolide HMR 3004

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