PMID- 11254686
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20220409
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 166
IP  - 7
DP  - 2001 Apr 1
TI  - In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of 
      hIL-6-transgenic mice with a hIL-6 receptor antagonist.
PG  - 4334-40
AB  - Neutralization of IL-6 represents an attractive therapeutic option in several 
      diseases, including B cell neoplasia, osteoporosis, and autoimmunity. Therapeutic 
      attempts in humans have shown that administration of injectable doses of a mAb to 
      IL-6 does not provide efficient neutralization of the cytokine in vivo. 
      Therefore, alternative approaches are needed. In this study, we evaluated whether 
      the Ab response to human IL-6 (hIL-6) elicited by vaccination with Sant1 (a hIL-6 
      variant with seven amino acid substitutions) was able to fully correct in vivo 
      the clinical and biological effects of a chronic endogenous overproduction of 
      hIL-6 in the hIL-6-transgenic NSE/hIL-6 mice. Because of the overexpression of 
      hIL-6, occurring since birth, with circulating levels in the nanogram per 
      milliliter range, NSE/hIL-6 mice have a marked decrease in growth rate, 
      associated with decrease in insulin-like growth factor I levels, and represent an 
      animal model of the growth impairment associated with human chronic inflammatory 
      diseases. Following immunization with Sant1, but not with hIL-6, NSE/hIL-6 mice 
      developed high titers of polyclonal Abs to hIL-6. The Abs, acquired by 
      transplacental transfer, effectively neutralized IL-6 activities in vivo as shown 
      by the complete correction of the growth defect and normalization of insulin-like 
      growth factor levels in the hIL-6-transgenic offspring. Immunization with Sant1 
      could therefore represent a novel and simple therapeutic approach for the 
      specific neutralization of IL-6 in humans.
FAU - De Benedetti, F
AU  - De Benedetti F
AD  - Dipartimento di Scienze Pediatriche, Instituto di Ricerca e Cura a Carattere 
      Scientifico Policlinico San Matteo, Universita' degli Studi di Pavia, Pavia, 
      Italy.
FAU - Pignatti, P
AU  - Pignatti P
FAU - Vivarelli, M
AU  - Vivarelli M
FAU - Meazza, C
AU  - Meazza C
FAU - Ciliberto, G
AU  - Ciliberto G
FAU - Savino, R
AU  - Savino R
FAU - Martini, A
AU  - Martini A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Recombinant Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Amino Acid Substitution/genetics/immunology
MH  - Animals
MH  - Animals, Newborn/genetics/growth & development/immunology
MH  - Antibody Formation/genetics
MH  - Down-Regulation/genetics/immunology
MH  - Female
MH  - Growth Disorders/genetics/immunology/prevention & control
MH  - Humans
MH  - Immunity, Maternally-Acquired
MH  - Immunization, Secondary
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Interleukin-6/*administration & dosage/biosynthesis/genetics/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic/*immunology
MH  - Phosphopyruvate Hydratase/genetics
MH  - Receptors, Interleukin-6/*antagonists & inhibitors
MH  - Recombinant Proteins/*administration & dosage/genetics/*immunology
MH  - Vaccination/*methods
EDAT- 2001/03/20 10:00
MHDA- 2001/06/22 10:01
CRDT- 2001/03/20 10:00
PHST- 2001/03/20 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/03/20 10:00 [entrez]
AID - 10.4049/jimmunol.166.7.4334 [doi]
PST - ppublish
SO  - J Immunol. 2001 Apr 1;166(7):4334-40. doi: 10.4049/jimmunol.166.7.4334.