Inflammatory responses in Ebola virus-infected patients.
Ebola virus subtype Zaire (Ebo-Z) induces acute haemorrhagic fever and a 60-80% mortality rate in humans. Inflammatory responses were monitored in victims and survivors of Ebo-Z haemorrhagic fever during two recent outbreaks in Gabon. Survivors were characterized by a transient release in plasma of interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNFalpha), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta early in the disease, followed by circulation of IL-1 receptor antagonist (IL-1RA) and soluble receptors for TNFalpha (sTNF-R) and IL-6 (sIL-6R) towards the end of the symptomatic phase and after recovery. Fatal infection was associated with moderate levels of TNFalpha and IL-6, and high levels of IL-10, IL-1RA and sTNF-R, in the days before death, while IL-1beta was not detected and MIP-1alpha and MIP-1beta concentrations were similar to those of endemic controls. Simultaneous massive activation of monocytes/macrophages, the main target of Ebo-Z, was suggested in fatal infection by elevated neopterin levels. Thus, presence of IL-1beta and of elevated concentrations of IL-6 in plasma during the symptomatic phase can be used as markers of non-fatal infection, while release of IL-10 and of high levels of neopterin and IL-1RA in plasma as soon as a few days after the disease onset is indicative of a fatal outcome. In conclusion, recovery from Ebo-Z infection is associated with early and well-regulated inflammatory responses, which may be crucial in controlling viral replication and inducing specific immunity. In contrast, defective inflammatory responses and massive monocyte/macrophage activation were associated with fatal outcome.
Baize
S
S
Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon, France. baize@cervi-lyon.inserm.fr
Leroy
E M
EM
Georges
A J
AJ
Georges-Courbot
M-C
MC
Capron
M
M
Bedjabaga
I
I
Lansoud-Soukate
J
J
Mavoungou
E
E
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000276:immunology; D005260:Female; D005681:Gabon / Q000453:epidemiology; D019142:Hemorrhagic Fever, Ebola / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D007700:Kinetics; D008297:Male; D011379:Prognosis; D017741:Survivors
D000893:Anti-Inflammatory Agents; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators