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. 2014 Feb 6;8(2):e2648.
doi: 10.1371/journal.pntd.0002648. eCollection 2014 Feb.

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality

Affiliations

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality

Elisabeth Astrup et al. PLoS Negl Trop Dis. .

Abstract

Background: Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10-20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome.

Methodology/principal findings: We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8.

Conclusions/significance: Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Plasma levels of inflammatory markers in scrub typhus patients and healthy controls.
Levels of inflammatory markers in scrub typhus patients (n = 129) on admission (A) and at recovery (R) as well as comparative levels in healthy controls (HC, n = 31) and infectious disease controls (ID, n = 31). Panel A shows levels of various chemokines, panel B levels of inflammatory cytokines, panel C levels of anti-inflammatory mediators and panel D markers of upstream inflammatory pathways. Data are given as medians and 25–75 percentiles. *p<0.05, **p<0.01 and ***p<0.001 versus healthy controls; †p<0.05, ††p<0.01 and †††p<0.001 versus infectious disease controls. Comparisons between levels at admission and recovery are also shown with p-values.
Figure 2
Figure 2. Plasma levels of inflammatory markers in scrub typhus patients in relation to disease severity.
Levels of inflammatory markers in scrub typhus patients (n = 129) on admission (A) and at recovery (R) in relation to disease severity where patients with no organ dysfunction were considered to have mild disease (n = 51, white boxes), those with one organ dysfunction moderate disease (n = 37, grey boxes), while two or more organ dysfunctions were defined as severe disease (n = 41, black boxes). Panel A shows levels of various chemokines, panel B levels of inflammatory cytokines, panel C levels of anti-inflammatory mediators and panel D markers of upstream inflammatory pathways. Data are given as medians and 25–75 percentiles. *p<0.05, **p<0.01 and ***p<0.001 versus mild disease; †p<0.05 and ††p<0.01 versus moderate disease.
Figure 3
Figure 3. Receiver operating characteristic (ROC) analysis showing associations between mortality and cytokine levels in scrub typhus patient on admission.
For each cytokine the AUC and standard error are given with corresponding p-value in parenthesis. Panel A: MCP-1, Monocyte chemoattractant protein-1; MIP-1β, Macrophage inflammatory protein-1β; RANTES, Regulated on Activation, Normal T Cell Expressed and Secreted; IL-8, interleukin-8; CCL-21, Chemokine (C-C motif) ligand-21. Panel B: TNF-α, Tumor necrosis factor-α; IL-6, interlukin-6; IL-10, interleukin-10; PTX-3, pentraxin 3; CRP, C-reactive protein.

References

    1. Watt G, Parola P (2003) Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 16 (5) 429–436. - PubMed
    1. Kawamura A Jr, Tanaka H (1988) Rickettsiosis in Japan. Jpn J Exp Med 58: 169–184. - PubMed
    1. Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, et al. (2006) Scrub typhus in Himalayas. Emerg Infect Dis 12: 1590–1592. - PMC - PubMed
    1. Varghese GM, Abraham OC, Mathai D, Thomas K, Aaron R, et al. (2006) Scrub typhus among hospitalised patients with febrile illness in South India: magnitude and clinical predictors. J Infect 52: 56–60. - PubMed
    1. Kumar K, Saxena VK, Thomas TG, Lal S (2004) Outbreak investigation of scrub Typhus in Himachal Pradesh (India). J Commun Dis 36: 277–283. - PubMed

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