Increased Il-8 Levels in the Cerebrospinal Fluid of Patients with Amyotrophic Lateral Sclerosis

Abstract

Inflammation has been implicated in the pathogenesis of many neurodegenerative diseases. The chemokine IL-8 is thought to have a pathophysiological role in neurodegenerative diseases. IL-8 has recently been shown to induce death of primary cultured motor neurons in vitro. We determined IL-8 levels in the cerebrospinal fluid (CSF) from 38 patients with sporadic amyotrophic lateral sclerosis (ALS) compared to patients with other non-inflammatory neurological diseases (cerebrovascular disease, degenerative dementia, Parkinson's disease, compressive radiculo-myelopathy). Multiple sclerosis (MS) patients were used as positive controls. The levels of IL-8 in the CSF of ALS patients were significantly higher than those of patients with other, non-inflammatory neurological conditions and similar to those of MS patients. The only variable influencing IL-8 in ALS patients was sex, with higher levels in men than in women. The presence of the inflammatory cytokine IL-8 in the CSF of patients with ALS at the time of diagnosis strengthens the hypothesis of a role for this chemokine in neurodegenerative disorders.

Chemokine Interleukin-8 (IL-8) in Alzheimer’s and Other Neurodegenerative Diseases

“…Analysis of lumbar puncture of CSF samples from ALS and controls has also identified IL-8 as a candidate biomarker for progression of the disease [25]. In another study IL-8 levels in CSF were compared between sporadic ALS patients and individuals with non-inflammatory disease [26]. Amounts of the chemokine were found to be significantly elevated in the ALS patients relative to controls and considerably higher in males compared to females.…”

Circulating cytokines and growth factors in professional soccer players: correlation with in vitro‐induced motor neuron death

“…A sustained inflammatory response and excessive production of cytokines by activated neuroglia are pathological events associated with the disease [2]. High levels of pro‐inflammatory cytokines, such as interleukin‐8 (IL‐8) [3], monocyte chemoattractant protein‐1 (MCP‐1) [4], interleukin‐6 (IL‐6) [5,6] and tumor necrosis factor‐α (TNF‐α) [7], have been reported in cerebro‐spinal fluid and sera of patients with ALS. A recent paper reported elevated plasma levels of the potent inflammatory mediator endotoxin/lipopolysaccharide in patients with sporadic ALS or Alzheimer’s disease (AD), compared to healthy subjects, with a close relationship to the clinical disease status in ALS [8].…”

Allergic Inflammation: Role of Cytokines with Special Emphasis on IL-4

“…In addition to a pro-inflammatory action through an increase in TH2 cytokine synthesis, T cells may serve a down-regulatory role. IL-4 is known to regulate the function of a variety of cells ofthe immune system (32). IL-4 has been previously shown to inhibit the synthesis of pro-inflammatory cytokines such as IL-1 beta and TNF alpha by LPSstimulated human peripheral blood mononuclear cells (33).…”

“…These pro-inflammatory cytokines are also produced in response to IL-2 and are thought to contribute to the toxicity associated with IL-2 immunotherapy (34). IL-4 is a potent regulator of IL-2-induced pro-inflammatory cytokine expression (32). Its suppressive effects are dependent on new protein synthesis and, in the case of IL-l beta, partly attributable to destabilization of cytokine mRNA (33).…”