Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome

Abstract

Objective and background: Pathological changes in severe acute respiratory syndrome (SARS) suggest that SARS sequelae are associated with dysregulation of cytokine and chemokine production. To improve understanding of the immuno-pathological processes involved in lung injury associated with SARS, the temporal changes in cytokine/chemokine profiles in the sera of SARS patients were compared with those of patients with community-acquired pneumonia (CAP), according to the degree of lung involvement.

Methods: Serum levels of 11 cytokines and chemokines, in 14 patients with SARS and 24 patients with CAP, were serially checked using a bead-based multiassay system. Sera from 12 healthy subjects were used as normal controls.

Results: The serum levels of interferon-gamma-inducible protein-10 (IP-10), IL-2 and IL-6 were significantly elevated during SARS infection. In patients with CAP, but not in those with SARS, the levels of interferon-gamma, IL-10, IL-8 and monokine induced by interferon-gamma (MIG) were significantly elevated compared with the levels in healthy controls. Among the chemokines/cytokines, IL-6 levels correlated most strongly with radiographic scores (r=0.62). The elevation of IP-10 and IL-2 antedated the development of chest involvement and reached peak levels earlier than the radiographic scores. In contrast, the dynamic changes in IL-6, C-reactive protein and neutrophils occurred synchronously with the changes in radiographic scores. The mean ratio of IL-6 to IL-10 in SARS patients (4.84; range 0.41-21) was significantly higher than that in CAP patients (2.95; range 0.02-10.57) (P=0.04).

Conclusions: The early induction of IP-10 and IL-2, as well as the subsequent over-production of IL-6 and lack of IL-10 production, probably contribute to the main immuno-pathological processes involved in lung injury in SARS. These changes in cytokine/chemokine profile are remarkably different from those observed in CAP patients.

Figure 1

Cytokine/chemokine profiles in the blood of patients with severe acute respiratory syndrome (SARS) and community‐acquired pneumonia (CAP). (a–k) Levels of the cytokines interferon (IFN)‐, tumour necrosis factor (TNF)‐, IL‐6, IL‐5, IL‐4, IL‐2, IL‐10; and the chemokines monocyte chemoattractant protein (MCP)‐1, monokine induced by IFN‐γ (MIG), IFN‐γ‐inducible protein‐10 (IP‐10) and IL‐8 in the blood of patients with SARS or CAP at different stages: A, admission; C, convalescent stage; N, normal control; P, progressive stage; W, worst stage. *P < 0.05 compared with normal control group. **P < 0.05 SARS (▪) versus CAP () groups.

Figure 2

Association between levels of interferon‐γ‐inducible protein‐10 (IP‐10) (a), IL‐2 (b), IL‐6 (c), CRP (d), neutrophil count (e), and lymphocyte count (f), and radiographic score during severe acute respiratory syndrome (SARS) infection. Data from all stages of SARS infection was pooled. Linear regression and correlation were analysed; r = correlation coefficient. CRP, C‐reactive protein.

Figure 3

Changes in the levels of interferon‐γ‐inducible protein‐10 (IP‐10) (a), IL‐2 (b), IL‐6 (c) and lymphocyte count (d) in the blood of patients with severe acute respiratory syndrome at different stages: A, admission; C, convalescent stage; N, normal control; P, progressive stage; W, worst stage. () Radiographic score; (—▴—) IP‐10; (—◆—) IL‐2; (—•—) IL‐6; (—▵—) lymphocyte.