Abstract
The immunopathogenesis of pediatric multiple sclerosis (MS) is not well understood. We studied the cytokine profile in pre-treatment serum specimens of 19 pediatric MS patients, 25 adult MS patients, and 22 age- and gender-matched pediatric healthy controls. In addition to IL-2, IL-12p40, IL-12p70, IL-18, IL-23, IL-6, TNF-α, TGF-β-1, IFN-γ, IL-17A, IL-21, IL-10, IL-4, IL-5, IL-13, and GM-CSF, we measured osteopontin and soluble VCAM-I. In children with MS, significantly lower levels of IL-6 were present compared to age- and gender-matched healthy control children (p < 0.05). Moreover, significantly higher levels of osteopontin (p < 0.02) and sVCAM-1 (p < 0.02) and lower levels of IL-6 (p < 0.01) were present, with trends toward lower levels of IL-12p70 (p = 0.074) and IL-17a (p = 0.05) compared to adults with MS. These findings indicate important differences in cytokine signatures in children with MS and suggest an unexpected possible lower inflammatory cytokine profile in children with MS.
Highlights
The immunopathogenesis of pediatric multiple sclerosis (MS) is not well understood
Comparison to healthy controls Lower levels of IL-6 were seen in patients with pediatric MS compared to pediatric healthy controls (p = 0.046)
Patients with pediatric MS had lower levels of GM-CSF, IFN-γ, IL-12p70, and IL-17A compared to healthy controls, but these differences were not identified as significantly different
Summary
The pathophysiology of multiple sclerosis (MS) is orchestrated by an array of molecular messengers known as cytokines. These signaling molecules are produced by or modulate the activity of T-cells and other immune cells. In serum and CSF studies of adult MS patients, elevations of proinflammatory IL-2, IL-12, IL-6, TNF-α, and IFN-γ, as well as anti-inflammatory/regulatory IL-10, IL-4, and TGF-β-1 cytokines, are identified [1]. A recent study by Martins et al of 833 adult subjects with MS and 117 healthy controls using a protocol similar to our study found elevations in pro-inflammatory IFN-γ, IL-2, IL-1B, and TNF-α, and anti-inflammatory IL-4, IL-10, and IL13 [2]. Higher levels of IL-18, IL-23, and IL-17 are seen in the serum of MS patients compared to healthy controls [3]
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