title: Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality.
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.
  
  
  RESULTS
  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
  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.
authors: Institute of Clinical Medicine, Akershus University Hospital, Lørenskog, Norway ; Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Elisabeth
authors: E
authors: Astrup
authors: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India.
authors: Jeshina
authors: J
authors: Janardhanan
authors: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Kari
authors: K
authors: Otterdal
authors: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Thor
authors: T
authors: Ueland
authors: Department of Microbiology, Christian Medical College, Vellore, Tamil Nadu, India.
authors: John A J
authors: JA
authors: Prakash
authors: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway ; Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Tove
authors: T
authors: Lekva
authors: Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway.
authors: Øystein A
authors: ØA
authors: Strand
authors: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India.
authors: O C
authors: OC
authors: Abraham
authors: Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India.
authors: Kurien
authors: K
authors: Thomas
authors: Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway ; Department of Infectious Diseases, St. Olav's Hospital, Trondheim, Norway.
authors: Jan Kristian
authors: JK
authors: Damås
authors: Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India.
authors: Prasad
authors: P
authors: Mathews
authors: Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India.
authors: Dilip
authors: D
authors: Mathai
authors: Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway ; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Pål
authors: P
authors: Aukrust
authors: Department of Medicine and Infectious Diseases, Christian Medical College, Vellore, Tamil Nadu, India.
authors: George M
authors: GM
authors: Varghese
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012612:Scrub Typhus / Q000097:blood / Q000453:epidemiology / Q000401:mortality
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016209:Interleukin-8