Volume 16, Number 1—January 2010
Dispatch
Acute Encephalopathy Associated with Influenza A Infection in Adults
, Chun Kwok Wong, Paul K.S. Chan, Niklas Lindegardh, Nicholas J. White, Frederick G. Hayden, Edward H.C. Wong, Ka Shing Wong, Clive S. Cockram, Joseph J.Y. Sung, and David S.C. HuiTable 2
Cytokine and chemokine concentrations in CSF and plasma samples from 3 patients with acute encephalopathy associated with influenza A infection, Prince of Wales Hospital, Hong Kong*
| Cytokine or chemokine | Reference range, pg/mL | CSF/plasma cytokine concentration, pg/mL (ratio) |
||
|---|---|---|---|---|
| Patient 1 | Patient 2 | Patient 3 | ||
| IL-6† | <3.1 | 8.0/6.3 (1.3) | 11.6/35.1 (0.3) | 2.2/5.9 (0.4) |
| CXCL8/IL-8‡ | <5.0 | 84.0/15.5 (5.4) | 74.8/13.8 (5.4) | 21.9/6.3 (3.5) |
| CXCL10/IP-10† | 202–1,480 | 15,374/102,019 (0.2) | 5,101/17,594 (0.3) | 1,371/1,550 (0.9) |
| CCL2/MCP-1‡ | < 10-57 | 996/82 (12.1) | 1,287/336 (3.8) | – |
| CXCL9/MIG | 48–482 | 11,58/14,001 (0.1) | 70/333 (0.2) | 145/1,019 (0.1) |
| IFN-γ | <15.6 | UD/14.4 | 4.7/10.1 | 0.4/2.0 |
| IL-12p70 | <7.8 | 1.5/UD | 1.3/UD | UD/UD |
| TNF-α | <10.0 | 1.7/1.4 | UD/1.2 | UD/UD |
| IL-10 | <7.8 | 2.5/2.2 | UD/7.3 | UD/1.7 |
| IL-1β | <3.9 | UD/UD | UD/3.7 | UD/UD |
| CCL5/RANTES | 4,382–18,783 | 4/2,507 | 14/1,609 | 1.3/814 |
*CSF, cerebrospinal fluid; –, test not done due to inadequate sample; UD, undetectable (i.e., below the detection limit of the cytokine/chemokine assay). Cytokines: Interleukin (IL)–1β, IL-6, IL-10, IL-12p70, tumor necrosis factor α (TNF-α). Chemokines: CXCL8/IL-8, monokine induced by interferon-γ (IFN- γ) (CXCL9/MIG), IFN-γ–inducible protein-10 (CXCL10/IP-10), monocyte chemoattractant protein–1 (CCL2/MCP-1), and regulated upon activation normal T cell–expressed and secreted (CCL5/RANTES). The plasma reference ranges are established from >100 healthy adults. The assay sensitivities of IL-1β, IL-6, IL-10, IL-12p70, TNF-α, IL8, MIG, IP-10, MCP-1, RANTES, and IFN-γ are 2.5, 3.3, 3.7, 1.9, 7.2, 0.2, 2.5, 2.8, 2.7, 1.0, and 7.1 pg/mL, respectively. Coefficients of variation are all <10%. In an earlier study involving 39 adult influenza patients hospitalized with cardio-respiratory complications (8), the median (interquartile range) plasma concentrations of IL-6, IL-8, IP-10, MCP-1, and MIG were 10.6 (4.2–18.4), 5.4 (2.5–8.7), 7,043.0 (4,025.1–1,2381.1), 76.5 (49.5-97.0), and 992.1 (499.1–1,992.3) pg/mL, respectively. In CSF, in subjects without neurologic disease/infection, these cytokines/chemokines are either undetectable or present at low levels (9–11). In a pediatrics influenza cohort, CSF cytokine levels were substantially higher in encephalopathy cases when compared to those with febrile seizure; CSF/plasma concentration was <1 (9).
†CSF cytokine concentrations above plasma reference ranges.
‡CSF/plasma cytokine concentration ratio consistently >3 (3.5–12.1), in addition to CSF cytokine concentrations being above the plasma reference ranges. For IFN-γ, IL-12p70, TNF-α, IL-10, IL-1β and RANTES, because of their low/undetectable levels, the CSF/plasma ratios were not calculated. CSF specimens from patients 1 and 2 were collected at the peak of symptoms, and before antiviral treatment (if given); CSF from patient 3 was collected when persistent tremor developed 18 hours after the ninth dose of oseltamivir; the drug was stopped afterward.
