Circulating tumour necrosis factor-α and interferon-γ are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue

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)-γ was associated with acute B19 virus infection (67%; P <0·0001) and follow-up (67%; P <0·0001). Detection of tumour necrosis factor (TNF)-α was associated with acute B19 virus infection (49%; P <0·0001) and follow-up (56%; P <0·0001). IL-1β 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-γ (⩾7 pg/ml) was associated with fatigue in those patients of ⩾15 years of age ( P =0·022). At follow-up, fatigue was associated with IFN-γ (⩾7 pg/ml) and/or TNF-α (⩾40 pg/ml) ( P =0·0275). Prolonged upregulation of serum IFN-γ and TNF-α appears to represent a consistent host response to symptomatic B19 virus infection.