Plasma IL‐8 and IL‐6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

Bont, Esjm de; Vellenga, Edo; Swaanenburg, Jcjm; Fidler, [No Value]; Brummen, PJ Visser-van; Kamps, WA

doi:10.1046/j.1365-2141.1999.01707.x

Cited by 77 publications

(62 citation statements)

References 43 publications

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“…9,12,14,15,20,36,37 IL-6 is an important component in the regulation of normal hematopoietic activity and its levels after transplantation have been widely determined, but IL-8 levels less so. We showed similar kinetics for IL-6 and IL-8, both reaching their peak levels on day +6 and preceding the hematologic recovery, as evaluated by the WBC (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

“…This was in agreement with previous reports which also showed maximal peak levels of the same cytokines around day +6 and a coordinate release of both, with a strong correlation between their plasma levels in the post-transplant period, as well as in non-hematological situations. 7,9,10,13,15,36 The synchronous wave of IL-8 and IL-6 secretion suggests that a similar mechanism underlies the production of these cytokines. Since IL-6 has no stimulatory effect on IL-8, the same agents are probably stimulating IL-6 and IL-8 production in parallel.…”

Section: Discussionmentioning

confidence: 99%

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Engraftment-associated hypophosphatemia – the role of cytokine release and steep leukocyte rise post stem cell transplantation

Raanani

Levi

Holzman

et al. 2001

Bone Marrow Transplant

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Summary:Hypophosphatemia associated with bone marrow transplantation has been infrequently reported. The suggested mechanism is phosphate uptake by the replicating cells. Various cytokines are associated with the development of hypophosphatemia. The present study evaluated the interrelationship between cytokine release, the rise in WBC and the development of hypophosphatemia during the engraftment period. Blood samples were obtained from 60 patients undergoing peripheral blood stem cell transplant, on the day of admission and then daily from the day of transplant until discharge. Hypophosphatemia developed in 62% of the patients. The median day of minimal phosphorus level was +8 and it antedated engraftment by 2 days. There was a significant correlation between the day of minimal phosphorus level and the day of maximal WBC and a significant correlation between the fall in phosphorus level and WBC rise. IL-6 and IL-8 showed similar kinetics. Higher IL-6 and IL-8 levels were directly associated with lower phosphorus levels. In conclusion, hypophosphatemia commonly occurs in the post-transplant period. We assume that both a direct effect of cytokine release and an increased consumption by the dividing WBCs contribute to its appearance. As its occurrence usually antedates engraftment it can be used as a forerunner for WBC recovery. Bone Marrow Transplantation (2001) 27, 311-317. Keywords: hypophosphatemia; cytokines; engraftment; transplantation; WBC Several conditions are known to induce moderate to severe hypophosphatemia (HP). They include low dietary intake, conditions associated with decreased absorption or increased urinary phosphate excretion and conditions associated with shifts of phosphate from the extracellular into the intracellular fluid. The latter include various cellular

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Engraftment-associated hypophosphatemia – the role of cytokine release and steep leukocyte rise post stem cell transplantation

Raanani

Levi

Holzman

et al. 2001

Bone Marrow Transplant

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“…27 Endothelial cells, such as the epithelial cells of the gut, play an important part in the innate immune system in neutropenic patients and produce IL-8 when exposed to bacteria. 28 Hence, perhaps monitoring IL-8 levels 29,30 combined with the MASCC risk score, when patients have low citrulline concentrations, might help distinguish those at risk of developing bacteraemia from those who are not.…”

Section: Discussionmentioning

confidence: 99%

Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients

Herbers

Blijlevens

Donnelly

et al. 2008

Bone Marrow Transplant

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Mucosal damage to the intestines induced by myeloablative conditioning for allogeneic PBSC transplant (PBSCT) can be determined by the concentration of citrulline, which is a functional marker of small intestinal enterocytes. Low citrulline concentrations in blood coincide with and are a response to severe mucosal barrier injury. We treated 29 patients with high-dose melphalan 200 mg/m 2 (Mel-200) to prepare for an autologous PBSCT and collected plasma samples from each patient starting before the myeloablative regimen and three times per week thereafter until discharge. The baseline citrulline concentration was 27.6 mM±4.0 (mean±95% confidence interval; CI), and citrulline concentrations declined rapidly thereafter reaching a nadir averaging 6.7 mM ± 2.7, 12 days after starting Mel-200. Citrulline concentrations, only increased gradually and were still low (12 mM ± 4) at discharge. A total of 20 patients developed fever, which was associated with bacteraemia in 10 cases. Their mean citrulline concentrations were lower at 5.5 mM ± 1.5 than were those of patients without bacteraemia (10.2 mM ± 3.9). Importantly, neither the number of preceding neutropenic days nor the mean C-reactive protein (CRP) concentration at the onset of fever was different between these two groups. In conclusion, citrulline concentrations rapidly decline after Mel-200 reflecting intestinal mucosal barrier injury. Low citrulline, rather than the duration of neutropenia, is associated with bacteraemia indicating the importance of an intact mucosal barrier in neutropenic patients.

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“…IL-6 is also reported to be present in the plasma earlier than C-reactive protein (25). Among cancer patients, IL-6 levels may be used to differentiate patients at low risk for septicemia (6).…”

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confidence: 99%

Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis

et al. 2005

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Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.

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Plasma IL‐8 and IL‐6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

Cited by 77 publications

References 43 publications

Engraftment-associated hypophosphatemia – the role of cytokine release and steep leukocyte rise post stem cell transplantation

Engraftment-associated hypophosphatemia – the role of cytokine release and steep leukocyte rise post stem cell transplantation

Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients

Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis

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