title: Serum cytokines associated with severity and complications of kala-azar.
abstract: OBJECTIVE
  Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar.
  
  
  METHODS
  We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n = 38) with patients without evidence of hemorrhage (n = 96). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC).
  
  
  RESULTS
  Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity.
  
  
  CONCLUSIONS
  In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.
authors.affiliation: Maternal and Childhood Department, Federal University of Piauí, Brazil.
authors.forename: Dorcas L
authors.initials: DL
authors.lastname: Costa
authors.forename: Regina L
authors.initials: RL
authors.lastname: Rocha
authors.forename: Rayssa M A
authors.initials: RM
authors.lastname: Carvalho
authors.forename: Adelino S
authors.initials: AS
authors.lastname: Lima-Neto
authors.forename: Michael O
authors.initials: MO
authors.lastname: Harhay
authors.forename: Carlos Henrique N
authors.initials: CH
authors.lastname: Costa
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Neto
authors.forename: Aldina P
authors.initials: AP
authors.lastname: Barral
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma