Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up

Abstract

Background: Expression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment.

Methods: From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR.

Results: Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-γ and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05).

Conclusions: IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.

Figure 1

Flow of patients through the study and data available for analysis.

Figure 2

Baseline levels of inflammatory cytokines in the cerebrospinal fluid (CSF) cells. Cytokines were measured in patients with Post-polio syndrome (PPS) and with other neurological diseases (OND). The median-based box plots indicate 25th/75th percentiles and whiskers indicate 5th/95th percentiles. Values of statistical significance are indicted (n.s.: non significant).

Figure 3

Baseline levels of inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs). Cytokines were measured in patients with post-polio syndrome (PPS) and with other neurological diseases (OND). The median-based box plots indicate 25th/75th percentiles and whiskers indicate 5th/95th percentiles. Values of statistical significance are indicted (n.s.: non significant).

Figure 4

Correlation study of pro-inflammatory cytokines in systemic and intrathecal compartments.

Figure 5

Combined levels of pro-inflammatory cytokines in the cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs). Tumor necrosis factor (TNF) and interferon γ (IFN-γ) were measured in patients with post-polio syndrome (PPS) and with other neurological diseases (OND). The median-based box plots indicate 25th/75th percentiles and whiskers indicate 5th/95th percentiles. Values of statistical significance are indicted (n.s.: non significant).

Figure 6

Effects of intravenous immunoglobulin (IVIG) on levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells. The median-based box plots indicate 25th/75th percentiles and whiskers indicate 5th/95th percentiles. Values of statistical significance are indicted (n.s.: non significant).

Figure 7

Effects of intravenous immunoglobulin (IVIG) on levels of inflammatory cytokines in peripheral blood mononuclear cells (PBMCs). The median-based box plots indicate 25th/75th percentiles and whiskers indicate 5th/95th percentiles. Values of statistical significance are indicted (n.s.: non significant).