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Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria

View Article: PubMed Central - PubMed

ABSTRACT

Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P < 0.001), interferon gamma (IFN-γ) (P = 0.0019), IL-2 (P = 0.0004), IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in sera than healthy controls. Patients with acute CM had significantly higher concentrations of IL-6 (P < 0.001) and IL-10 (P = 0.0003) than those presenting with acute SMA. Our findings are consistent with the concept that high levels of proinflammatory cytokines, despite high levels of the anti-inflammatory cytokine IL-10, could contribute to the pathogenesis of CM.

No MeSH data available.


Related in: MedlinePlus

(A to J) Plots of log-transformed concentrations (picograms per milliliter) of different cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12p70) in serum samples collected from healthy controls (Control) and from patients with acute uncomplicated malaria (UCM), acute severe malarial anemia (SMA), and acute cerebral malaria (CM). (K and L) Plots of the ratios of log-transformed IL-10 to TNF-α and IL-10 to IL-6, respectively, during acute infection, showing medians and 10th and 90th percentiles.
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Figure 1: (A to J) Plots of log-transformed concentrations (picograms per milliliter) of different cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12p70) in serum samples collected from healthy controls (Control) and from patients with acute uncomplicated malaria (UCM), acute severe malarial anemia (SMA), and acute cerebral malaria (CM). (K and L) Plots of the ratios of log-transformed IL-10 to TNF-α and IL-10 to IL-6, respectively, during acute infection, showing medians and 10th and 90th percentiles.

Mentions: The median concentration of IFN-γ (Fig. 1A; see also Table S1 in the supplemental material) was significantly (P = 0.0019) higher in acute CM cases (17.3 pg/ml) than in controls (2.32 pg/ml) and in acute SMA (P = 0.0248) and acute UCM (P = 0.0295) cases, and these levels then decreased significantly (P < 0.001) in convalescence (Fig. 2A). TNF-α levels during acute disease were higher in all types of clinical malaria than in controls (Fig. 1B), with significant (P = 0.0313 for UCM, P = 0.0060 for SMA, and P = 0.0391 for CM) differences observed between CM patients (median, 3.76 pg/ml) and controls (median, 1.41 pg/ml) and between SMA patients (median, 2.95 pg/ml) and controls. UCM patients also had significantly (P = 0.0012) higher TNF-α levels (2.12 pg/ml) than controls (1.41 pg/ml) but significantly (P = 0.0006) lower levels than CM cases (median, 3.76 pg/ml). TNF-α levels decreased significantly in convalescence (Fig. 2B) for both CM (median, 3.76 pg/ml, falling to 1.69 pg/ml; P = 0.0002) and SMA (median, 2.95 pg/ml, falling to 1.80 pg/ml; P = 0.0020).


Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria
(A to J) Plots of log-transformed concentrations (picograms per milliliter) of different cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12p70) in serum samples collected from healthy controls (Control) and from patients with acute uncomplicated malaria (UCM), acute severe malarial anemia (SMA), and acute cerebral malaria (CM). (K and L) Plots of the ratios of log-transformed IL-10 to TNF-α and IL-10 to IL-6, respectively, during acute infection, showing medians and 10th and 90th percentiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382826&req=5

Figure 1: (A to J) Plots of log-transformed concentrations (picograms per milliliter) of different cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL-12p70) in serum samples collected from healthy controls (Control) and from patients with acute uncomplicated malaria (UCM), acute severe malarial anemia (SMA), and acute cerebral malaria (CM). (K and L) Plots of the ratios of log-transformed IL-10 to TNF-α and IL-10 to IL-6, respectively, during acute infection, showing medians and 10th and 90th percentiles.
Mentions: The median concentration of IFN-γ (Fig. 1A; see also Table S1 in the supplemental material) was significantly (P = 0.0019) higher in acute CM cases (17.3 pg/ml) than in controls (2.32 pg/ml) and in acute SMA (P = 0.0248) and acute UCM (P = 0.0295) cases, and these levels then decreased significantly (P < 0.001) in convalescence (Fig. 2A). TNF-α levels during acute disease were higher in all types of clinical malaria than in controls (Fig. 1B), with significant (P = 0.0313 for UCM, P = 0.0060 for SMA, and P = 0.0391 for CM) differences observed between CM patients (median, 3.76 pg/ml) and controls (median, 1.41 pg/ml) and between SMA patients (median, 2.95 pg/ml) and controls. UCM patients also had significantly (P = 0.0012) higher TNF-α levels (2.12 pg/ml) than controls (1.41 pg/ml) but significantly (P = 0.0006) lower levels than CM cases (median, 3.76 pg/ml). TNF-α levels decreased significantly in convalescence (Fig. 2B) for both CM (median, 3.76 pg/ml, falling to 1.69 pg/ml; P = 0.0002) and SMA (median, 2.95 pg/ml, falling to 1.80 pg/ml; P = 0.0020).

View Article: PubMed Central - PubMed

ABSTRACT

Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-&alpha;) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-&alpha; (P &lt; 0.001), interferon gamma (IFN-&gamma;) (P = 0.0019), IL-2 (P = 0.0004), IL-6 (P &lt; 0.001), IL-8 (P &lt; 0.001), and IL-10 (P &lt; 0.001) in sera than healthy controls. Patients with acute CM had significantly higher concentrations of IL-6 (P &lt; 0.001) and IL-10 (P = 0.0003) than those presenting with acute SMA. Our findings are consistent with the concept that high levels of proinflammatory cytokines, despite high levels of the anti-inflammatory cytokine IL-10, could contribute to the pathogenesis of CM.

No MeSH data available.


Related in: MedlinePlus