Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids - PubMed (original) (raw)

Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids

B M Jones et al. Clin Exp Immunol. 2004 Mar.

Abstract

Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen-stimulated cytokine-secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme-linked immunospot technology. Numbers of interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)-stimulated IL-10 secreting cells were increased in early SARS but fell during treatment. SAC-induced IL-12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL-6 and tumour necrosis factor-alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti-inflammatory and antiviral therapies in order to limit cytokine impairment.

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Figures

Fig. 1

Fig. 1

Steroid doses (mg/day) in patients with SARS. Each point represents the dose and drug for an individual patient on the days they were evaluated for cytokine production. Open circles indicate no treatment, closed circles prednisolone, open squares methylprednisolone.

Fig. 2

Fig. 2

Changes over time of PHA-induced IFN-γ, IL-2, IL-4, IL-10 and IL-12-secreting cells (ELISPOTS/106 PBM or ELISPOTS/106 T cells) in patients with SARS. Normal control values (5–95 percentiles of 60 healthy subjects) are indicated as horizontal dotted lines. Open circles are results obtained before starting steroid treatment. Curves were fitted by non-linear regression using GraphPad Prism version 4·00 for Windows, GraphPad Software, San Diego, CA, USA,

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Fig. 3

Fig. 3

Changes over time of unstimulated and SAC-induced IL-10 and IL-12-secreting cells (ELISPOTS/106 PBM) in SARS patients. See legend to Fig. 2 for explanation of symbols.

Fig. 4

Fig. 4

Changes over time of unstimulated, PHA-stimulated and SAC-stimulated IL-6 and TNF-α-secreting cells (ELISPOTS/106 PBM) in patients with SARS. Horizontal arrows indicate patients with poor outcome. See legend to Fig. 2 for explanation of symbols.

Fig. 5

Fig. 5

Changes over time of leucocyte and lymphocyte subset counts in patients with SARS. Curves were fitted by non-linear regression using GraphPad Prism™ software.

Comment in

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