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

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)-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.