title: Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue.
abstract: To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50). At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months). In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275). Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.
authors.affiliation: Department of Microbiology, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK1.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Kerr
authors.affiliation: Department of Virology2, North Western Injury Research Centre5 and School of Biological Sciences6, University of Manchester, Manchester, UK.
authors.forename: Faraj
authors.initials: F
authors.lastname: Barah
authors.affiliation: Staffordshire Rheumatology Centre, Stoke-on-Trent, UK3.
authors.forename: Derek L
authors.initials: DL
authors.lastname: Mattey
authors.affiliation: Department of Biochemistry, Manchester Royal Infirmary, Manchester, UK4.
authors.forename: Ian
authors.initials: I
authors.lastname: Laing
authors.affiliation: Department of Virology2, North Western Injury Research Centre5 and School of Biological Sciences6, University of Manchester, Manchester, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hopkins
authors.affiliation: Department of Virology2, North Western Injury Research Centre5 and School of Biological Sciences6, University of Manchester, Manchester, UK.
authors.forename: Ian V
authors.initials: IV
authors.lastname: Hutchinson
authors.affiliation: Formerly of the MRC Common Cold Unit, Salisbury, Wiltshire, UK(now closed)7.
authors.forename: David A J
authors.initials: DAJ
authors.lastname: Tyrrell
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003289:Convalescence; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010322:Parvoviridae Infections / Q000097:blood / Q000150:complications* / Q000821:virology; D017992:Parvovirus; D012217:Rheumatoid Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D012217:Rheumatoid Factor