Cobalamin (vitamin B(12)) positively regulates interleukin-6 levels in rat cerebrospinal fluid.
We have previously demonstrated that the repeated intracerebroventricular (i.c.v.) microinjection of interleukin-6 (IL-6) prevented the myelinolytic lesions of cobalamin-deficient (Cbl-D) central neuropathy [or subacute combined degeneration (SCD)] in totally gastrectomized (TGX) rats. We therefore hypothesized that cobalamin (Cbl) may actually regulate IL-6 levels in rat cerebrospinal fluid (CSF). We measured IL-6 levels in the CSF of rats made Cbl-D by means of total gastrectomy (TG) or chronic feeding with a Cbl-D diet and killed at different times from the beginning of the experiment, and found that IL-6 levels significantly and progressively decreased over time. Chronic 2-month Cbl administration started 1 week after surgery prevented the decrease in IL-6 levels and, when it was started 2 months after surgery, it significantly increased IL-6 levels, but not to presurgical values. We also investigated whether IL-6 decrease might be ultimately due to the Cbl-deficiency-linked decrease in epidermal growth factor (EGF) synthesis. Repeated i.c.v. administrations of EGF to TGX rats did not modify CSF IL-6 levels. These results, together with those of a previous study showing the preventive effect of IL-6 treatment on SCD lesions, demonstrate that: (i) Cbl selectively regulates CSF IL-6 levels; and (ii) decreased IL-6 availability plays a role in the pathogenesis of the experimental SCD, in which no evidence of inflammatory and/or immunological reaction has been observed.
Scalabrino
Giuseppe
G
Institute of General Pathology, University of Milan, Via Mangiagalli 31, 20133 Milan, Italy. giuseppe.scalabrino@unimi.it
Corsi
M M
MM
Veber
D
D
Buccellato
F R
FR
Pravettoni
G
G
Manfridi
A
A
Magni
P
P
D000818:Animals; D004815:Epidermal Growth Factor / Q000134:cerebrospinal fluid / Q000494:pharmacology; D005743:Gastrectomy; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000134:cerebrospinal fluid*; D020738:Leptin / Q000134:cerebrospinal fluid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014805:Vitamin B 12 / Q000494:pharmacology*; D014806:Vitamin B 12 Deficiency / Q000134:cerebrospinal fluid / Q000276:immunology
D015850:Interleukin-6; D020738:Leptin; D004815:Epidermal Growth Factor; D014805:Vitamin B 12