Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis.
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.


METHODS
We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.


RESULTS
MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075).


CONCLUSIONS
We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.
Kuhle
J
J
Department of Neurology, University Hospital Basel, Basel, Switzerland.
Lindberg
R L P
RL
Regeniter
A
A
Mehling
M
M
Steck
A J
AJ
Kappos
L
L
Czaplinski
A
A
D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D018450:Disease Progression; D042241:Early Diagnosis; D005911:Gliosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016209:Interleukin-8