Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions*1

Hartung, Thomas; Doecke, Wolf Dietrich; Bundschuh, Daniela S.; Foote, Mary Ann; Gantner, Florian; Hermann, Corinna; Lenz, André; Milwee, Steven; B, Rich; Simon, Bernadett; Volk, Hans‐Dieter; Aulock, Sonja von; Wendel, Albrecht

doi:10.1053/cp.1999.v66.a101210

Cited by 63 publications

(43 citation statements)

References 28 publications

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“…46,47 Th2 and DC2 polarization were found in healthy volunteers treated with filgrastim in vivo or in peripheral blood incubated with filgrastim in vitro, [48][49][50] supporting the expectation that the risk of chronic GVHD would be increased with the use of filgrastim-mobilized blood stem cells for allogeneic transplantation. We here describe a population of patients with chronic GVHD, the high-risk subgroup, some of whom had typical manifestations of both acute (eg, maculopapular rash and inflammatory diarrhea) and chronic (eg, lichenoid changes of the oral mucosa) GVHD.…”

Section: Discussionmentioning

confidence: 76%

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

Przepiorka

Anderlini

Saliba

et al. 2001

Blood

266

233

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The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P ‫؍‬ .001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P ‫؍‬ .046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P < .001) and treatment failure (HR, 5.2; P < .001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome. (Blood. 2001;98:1695-1700)

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Section: Discussionmentioning

confidence: 76%

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

Przepiorka

Anderlini

Saliba

et al. 2001

Blood

266

233

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“…Although exogenous administration of G-CSF has not been associated with improved outcomes in patients with pneumonia and/or severe sepsis in large clinical trials (310,311,361), melioidosis may differ from infections due to other organisms because of the key role of neutrophils in patients with recognized risk factors for neutrophil defects. G-CSF may reverse these defects (312), act to counter inflammatory cytokines (187,471), and increase intracellular concentrations of antibiotics (131,248,298). The use of G-CSF in patients with septic shock due to melioidosis was associated with a large fall in mortality (from 95 to 10%); however, several confounding factors may at least partly account for this effect (84).…”

Section: Management Of Sepsis Syndromementioning

confidence: 99%

Melioidosis: Epidemiology, Pathophysiology, and Management

2005

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Melioidosis, caused by the gram-negative saprophyte Burkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain of B. pseudomallei has recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease

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“…G-CSF has been shown to inhibit the secretion of Th1 cytokines by T cells, thus polarizing them toward a Th2 cytokine (IL-4 and IL-10) phenotype (9,12,13,15,59). We (our unpublished results) and others have also demonstrated that G-CSF suppresses responsiveness of conventional T cells, resulting in impairments in the ability of T cells to proliferate, and to differentiate in response to IL-2, mitogens (PHA and Con A), and allo-Ags (14, 16, 18, 20, 59 -62).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Modulates α-Galactosylceramide-Responsive Human Vα24+Vβ11+ NKT Cells

Crough

Nieda

Nicol

2004

The Journal of Immunology

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Despite more than a 10-fold increase in T cell numbers in G-CSF-mobilized peripheral blood stem cell (PBSC) grafts, incidence and severity of acute graft-vs-host disease (GVHD) are comparable to bone marrow transplantation. As CD1d-restricted, Vα24+Vβ11+ NKT cells have pivotal immune regulatory functions and may influence GVHD, we aimed to determine whether G-CSF has any effects on human NKT cells. In this study, we examined the frequency and absolute numbers of peripheral blood NKT cells in healthy stem cell donors (n = 8) before and following G-CSF (filgrastim) treatment. Effects of in vivo and in vitro G-CSF on NKT cell cytokine expression profiles and on responsiveness of NKT cell subpopulations to specific stimulation by α-galactosylceramide (α-GalCer) were assessed. Contrary to the effects on conventional T cells, the absolute number of peripheral blood NKT cells was unaffected by G-CSF administration. Furthermore, responsiveness of NKT cells to α-GalCer stimulation was significantly decreased (p < 0.05) following exposure to G-CSF in vivo. This hyporesponsiveness was predominantly due to a direct effect on NKT cells, with a lesser contribution from G-CSF-mediated changes in APC. G-CSF administration resulted in polarization of NKT cells toward a Th2, IL-4-secreting phenotype following α-GalCer stimulation and preferential expansion of the CD4+ NKT cell subset. We conclude that G-CSF has previously unrecognized differential effects in vivo on NKT cells and conventional MHC-restricted T cells, and effects on NKT cells may contribute to the lower than expected incidence of GVHD following allogeneic peripheral blood stem cell transplantation.

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Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions*1

Cited by 63 publications

References 28 publications

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation

Melioidosis: Epidemiology, Pathophysiology, and Management

Granulocyte Colony-Stimulating Factor Modulates α-Galactosylceramide-Responsive Human Vα24+Vβ11+ NKT Cells

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