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Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea.

Zulu I, Hassan G, Njobvu R N L, Dhaliwal W, Sianongo S, Kelly P - BMC Infect. Dis. (2008)

Bottom Line: Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends.These factors were better predictors of survival than BMI.Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Gastroenterology and Nutrition group, Department of Medicine, University of Zambia School of Medicine, Lusaka, Zambia. zuluisaac@yahoo.com

ABSTRACT

Background: Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality.

Methods: Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-gamma and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up.

Results: Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-gamma, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis.

Conclusion: High serum concentrations of TNFR p55, IFN-gamma, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

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The box plots show median, interquartile range, and range of serum concentrations of sTNFR p55 (1A), IFN-γ (1B) and CRP (1C) in groups 1–5.
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Figure 1: The box plots show median, interquartile range, and range of serum concentrations of sTNFR p55 (1A), IFN-γ (1B) and CRP (1C) in groups 1–5.

Mentions: Serum cytokines and CRP were all readily detected in sera from the five groups, except for IL-12 which was below the threshold of detection of the assay in all samples tested and is therefore not discussed further. Concentrations of TNFRp55 (p < 0.0001), MIF (p < 0.005), IL-6 (p < 0.01), IFN-γ (p < 0.01), and CRP (p < 0.0001) all showed significant trends across all groups (Fig 1). Only TNFRp55 (p = 0.0001), interferon-γ (p = 0.0007) and CRP (p = 0.0001) were significantly greater in group 5 than in the other groups. This remained true if only patients with diarrhoea were considered: the significance or non-significance of each cytokine remained the same. As expected, BMI was lower in patients who died (16.2 kg/m2, SD 2.9) than in survivors (20.0 kg/m2, SD 4.9; p = 0.0006)


Cytokine activation is predictive of mortality in Zambian patients with AIDS-related diarrhoea.

Zulu I, Hassan G, Njobvu R N L, Dhaliwal W, Sianongo S, Kelly P - BMC Infect. Dis. (2008)

The box plots show median, interquartile range, and range of serum concentrations of sTNFR p55 (1A), IFN-γ (1B) and CRP (1C) in groups 1–5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2605754&req=5

Figure 1: The box plots show median, interquartile range, and range of serum concentrations of sTNFR p55 (1A), IFN-γ (1B) and CRP (1C) in groups 1–5.
Mentions: Serum cytokines and CRP were all readily detected in sera from the five groups, except for IL-12 which was below the threshold of detection of the assay in all samples tested and is therefore not discussed further. Concentrations of TNFRp55 (p < 0.0001), MIF (p < 0.005), IL-6 (p < 0.01), IFN-γ (p < 0.01), and CRP (p < 0.0001) all showed significant trends across all groups (Fig 1). Only TNFRp55 (p = 0.0001), interferon-γ (p = 0.0007) and CRP (p = 0.0001) were significantly greater in group 5 than in the other groups. This remained true if only patients with diarrhoea were considered: the significance or non-significance of each cytokine remained the same. As expected, BMI was lower in patients who died (16.2 kg/m2, SD 2.9) than in survivors (20.0 kg/m2, SD 4.9; p = 0.0006)

Bottom Line: Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends.These factors were better predictors of survival than BMI.Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tropical Gastroenterology and Nutrition group, Department of Medicine, University of Zambia School of Medicine, Lusaka, Zambia. zuluisaac@yahoo.com

ABSTRACT

Background: Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality.

Methods: Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-gamma and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up.

Results: Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-gamma, CRP and low CD4 count (CD4 count <100) were predictive of mortality. Although nutritional status (assessed by body mass index, BMI) was predictive in univariate analysis, it was not an independent predictor in multivariate analysis.

Conclusion: High serum concentrations of TNFR p55, IFN-gamma, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-gamma and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.

Show MeSH
Related in: MedlinePlus