Cytokine responses in acute and persistent human parvovirus B19 infection

Abstract

The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response correlated with the previously identified sustained CD8+ T cell response and viraemia. A cross-sectional study on patients with persistent B19 infection showed no apparent imbalance of their cytokine pattern, except for an elevated level of IFN-gamma response. No general immunodeficiency was diagnosed as an explanation for the viral persistence in this later group. Neither the acutely infected nor the persistently infected patients demonstrated a Th2 cytokine response. In conclusion, the acutely infected patients demonstrated a sustained Th1 cytokine response whereas the persistently infected patients did not exhibit an apparent imbalance of their cytokine pattern except for an elevated IFN-gamma response.

Fig. 1

Proinflammatory cytokine levels in serum of acutely B19-infected individuals. Concentration of the proinflammatory cytokines tumour necrosis factor-α, interleukin (IL)-1β, granulocyte–macrophage colony-stimulating factor, IL-6, interferon-γ and chemokine IL-8 as well as B19 viral load in serum is shown for two acutely B19-infected individuals (a) P7 and (b) P2. The time-points designate number of weeks after onset of symptoms.

Fig. 2

T helper (Th)1 cytokine levels in serum of acutely B19-infected individuals. Concentrations of the Th1 cytokines interleukin (IL)-2, IL-12, IL-15 and interferon (IFN)-γ are shown for three patients: (a) P2 and (b) P3 and (c) P1. The B19 viral load in serum is shown as DNA copies/ml. Mean levels of IL-2, IL-12, IL-15 and IFN-γ for the healthy seropositive controls were 106, 125, 505 and 5 pg/ml, respectively.

Fig. 3

Interferon (IFN)-γ levels of acutely and persistently B19-infected individuals. The concentrations of IFN-γ were compared between the different study groups. Acute: group I, acutely infected individuals (n = 8). The acute early sample was collected within 1–5 weeks of symptom appearance. The acute late sample was collected after 20–130 weeks of follow-up. Persistently infected: group II, persistently infected individuals (n = 22). Ctrl: healthy: group III, healthy B19-seropositive individuals (n = 18).