Circulating igm antibodies against myelin basic protein in health and multiple sclerosis A possible

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Circulating igm antibodies against myelin basic protein in health and multiple sclerosis
A possible component in the regulation of self-reactivity?
Hedegaard, Chris Juul; Sellebjerg, F.; Bendtzen, K.; Nielsen, C. H.
Published in:
Inflammation Research
Publication date:
2007
Document Version
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Citation (APA):
Hedegaard, C. J., Sellebjerg, F., Bendtzen, K., & Nielsen, C. H. (2007). Circulating igm antibodies against myelin
basic protein in health and multiple sclerosis: A possible component in the regulation of self-reactivity?
Inflammation Research, 56(Suppl. 3), S469.

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and investigate your claim.
8th World Congress on
Inflammation
16–20 June 2007
Copenhagen Conference Center
(Bella Center, Copenhagen, Denmark)
The Abstracts
List of Committees
Congress President Steering Committee
Ian Ahnfelt-Rønne, Denmark Gordon Letts, USA
Ian Adcock, UK
Ian Ahnfelt-Rønne, Denmark
Congress Organising Committee
Charles Brink, France
Michel Chignard, France
Ian Ahnfelt-Rønne, Denmark
John Hamilton, Australia
Ben Vainer, Denmark
Lisa Marshall, USA
Børge Diderichsen, Denmark
Kouji Matsushima, Japan
Heikki Vapaatalo, Finland
Tineke Meijers, Canada
Helle Markholst, Denmark
Wim van den Berg, The Netherlands
Jørgen Rask Madsen, Denmark
Tatsutoshi Nakahata, Japan
Klaus Bendtzen, Denmark
Lars Fugger, Denmark
Kouji Matsushima, Japan
Lars K. Poulsen, Denmark
Niels Borregaard, Denmark
Ole Haagen Nielsen, Denmark
Peter Riis Hansen, Denmark
Rikard Holmdahl, Sweden
Roland Jonsson, Norway
Thomas Kongstad Petersen, Denmark
Uffe Bang Olsen, Denmark
Zhanguo Li, China
Regina Emuzyte, Lithuania
Contents
Oral Communications
Saturday 16 June 2007
Abstract No. Page Title
Evening PL01 S343 Plenary 1:
Jules Hoffmann
Sunday 17 June 2007
Abstract No. Page Title
Morning PL02 S343 Plenary 2:
Lars Fugger
S01.1-S01.3 S343 Symposium 1:
Autoimmunity
S02.1-S02.4 S345 Symposium 2:
Intersection of cancer and inflammation
S03.1-S03.5 S346 Symposium 3:
Inflammation associated tissue damage,
repair and regeneration medicine
Afternoon FG01.1-FG01.8 S348 Focus Group 1:
Proteases in inflammation
FG02.1-FG02.5 S349 Focus Group 2:
Inflammatory bowel disease (IBD)
FG03.1-FG03.3 S351 Focus Group 3:
Immunogenicity of protein therapeutics
in chronic inflammation
FG04.1-FG04.5 S355 Focus Group 4:
Coagulation and inflammation
FC01.1-FC01.7 S357 Free Communications 1:
Inflammation and the nervous system
Monday 18 June 2007
Abstract No. Page Title
Morning PL03 S400 Plenary 3:
Andreas Radbruch
S04.1-S04.4 S360 Symposium 4:
Inflammation and rheumatic diseases
S05.1-S05.4 S361 Symposium 5:
Immunology of TypeI diabetes
S06.1-S06.4 S362 Symposium 6:
Dermatology and inflammation
Afternoon FC12.1-FC12.6 S404 Free Communications 12:
Genetics
FC02.1-FC02.10 S364 Free Communications 2:
Allergy
FC03.1-FC03.9 S368 Free Communications 3:
Arthritis
FC04.1-FC04.8 S372 Free Communications 4:
Signal transduction
FC05.1-FC05.8 S375 Free Communications 5:
Chemokines and cytokines
Tuesday 19 June 2007
Abstract No. Page Title
Morning PL04 S378 Plenary 4:
Gçran Hansson
S07.1-S07.4 S379 Symposium 7:
Inflammation and the vascular wall
S08.1-S08.4 S380 Symposium 8:
Genetics and genomics of inflammation
S09.1-S09.4 S381 Symposium 9:
Allergicinflammation
Afternoon FG05.1-FG05.7 S382 Focus Group 5:
The role of human secreted phospholipases A2 ininflammation:
the link to atherogenesis
FC06.1-FC06.8 S385 Free Communications 6:
Circulation
FC07.1-FC07.8 S388 Free Communications 7:
General inflammation (I)
FC08.1-FC08.8 S391 Free Communications 8:
Tissue damage
FC09.1-FC09.8 S394 Free Communications 9:
Skin inflammation
FC10.1-FC10.7 S397 Free Communications 10:
General inflammation (II)
Wednesday 20 June 2007
Abstract No. Page Title
PL05 – Plenary 5:
Salvador Moncada (no abstract available)
FC11.1-FC11.8 S401 Free Communications 11:
Novel therapeutic approaches
Posters
Sunday 17 June 2007 morning to Tuesday 19 June 2007 afternoon
Abstract No. Page
P01.1-P12.20 S406
Mini-papers for Young Investigator Award Competition
Monday 18 June 2007
Page Title
Afternoon Mini-paper 1 S481 Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor counteracts
immobilization stress- induced alterations indifferent behavioral and
biochemical parameters in mice
Mini-paper 2 S488 PAF-induced kinin B receptor in vivo up-regulation:
1
involvement of distinct kinase pathways
Mini-paper 3 S492 A role for hydrogen peroxide ininflammatory hyperalgesia
of the mouse hindpaw
Mini-paper 4 S495 Strain differences in peritoneal macrophage activity and
susceptibility to experimentalallergic encephalomyelitis inductionin rats
Mini-paper 5 S499 Kallikrein-mediatedactivation of PARs in inflammation and nociception
Mini-paper 6 S503 Substance P and CGRP do not play animportant role
in TNFa-induced inflammation
Author Index S508
Oral Communications and
Posters
Inflamm.Res., Supplement 3 (2007) S343
PL01 sclerosisbrains,andcellspresentinganimmunodominant
MBP(85-99) peptide in complex with HLA-DR2b have
THE ANTIMICROBIAL DEFENSE OF been shown to be present in multiple sclerosis lesions.
DROSOPHILIA: A PARADIGM FOR INNATE Also, humanized mice expressing the HLA-DR2b gene
IMMUNITY and a human T-cell receptor (TCR) that recognises the
MBP85-99 peptide in the context of HLA-DR2b either
Jules Hoffman spontaneously or after immunization with MBP85-99
develop experimental autoimmune encephalomyelitis,
Jules Hoffmann, Institute of Molecular and Cellular which has several features in common with multiple
Biology, Strasbourg,France sclerosis. This talk will focus on, how humanized mice
recently has been used to study the interplay between
The Drosophila host defense is a multifaceted process genetic and environmental risk factors in multiple scle-
which involves reprogramming of gene expression, acti- rosis.
vationofproteolyticcascadesinthebloodanduptakeof
microrganismsby professionalphagocytes. Most of the Contact information: Dr Lars Fugger, MRC Human
recentstudieshavefocusedonchallenge-inducedexpres- ImmunologyUnitandDepartmentofClinicalNeurology,
sion of antimicrobial peptides and have addressed the WeatherallInstituteofMolecularMedicine,JohnRadcliffe
following questions : (1) which genes are upregulated Hospital, University of Oxford,UK
duringvarioustypesofbacterial,fungalorviralinfections
andwhataretheirfunctions?(2),whatisthenatureofthe E-mail: [email protected]
intracellular signalling cascades which lead togene tran-
scription during these infections; (3) how does Droso-
phila recognize infections and does it discriminate S01.1
between various types of aggressors (e.g. fungal versus
bacterial or viral) to mount an appropriate response. RHEUMATOID ARTHRITIS; FROM DISEASE TO
Overthelasttenyearswehavegainedsignificantinsights GENES AND BACK - FOLLOWING AN
intothesevariousaspectsandthepresentationwillreview OXIDATION PATH
our current understanding of the Drosophila immune
response and put it into a phylogenetic perspective, RikardHolmdahl
namely by drawing some stringent parallels with the
mammalian innate immuneresponse. Medical InflammationResearch, Lund University, Lund,
Sweden
Recent Reviews: Lemaitre B., Hoffmann J.A. The Host
Defense of Drosophila melanogaster. Annu. Rev. To resolve the pathogenic mechanisms of rheumatoid
Immunol. 2007, 25: 697-743 Hoffmann, J.A., Ferrandon, arthritis (RA) we need to identify the causative genetic
D.,Imler,J.L.,C.Hetru.ImmuneSensingandSignalling andenvironmentalfactors.Thishashoweverproventobe
during Bacterial and Fungal Infections in Drosophila. complex,withmanyfactorsandgenesinteracting.Inbred
Natyre Reviews Immunol. 2007, In Press animals are useful for studies of the identification of
genesassociatedwithcomplextraitsanddiseasessuchas
Contact information: Mr Jules Hoffmann, Jules RA.Animalmodelsofferapossibilitytobetterdefinethe
Hoffmann, Institute of Molecular and Cellular Biology, traits, and to segregate the genes in a controlled way
Strasbourg,France enabling linkage analysis. There are several arthritis
E-mail: [email protected] models, which each may reflect various variants of the
heterogeneity of RA in humans. Examples are collagen
induced arthritis (CIA) and pristane induced arthritis
PL02 (PIA), which both fulfills the clinical diagnostic criteria
for RA. Both diseases are genetically complex and the
GENETIC AND ENVIRONMENTAL RISK susceptibilityis,asRA,dependentonmanypolymorphic
FACTORS IN MULTIPLE SCLEROSIS genesoperatinginconcert. Sofar2genesinthisconcert
have been identified; the MHC class II Ab gene in the
Lars Fugger mouse (1) and the Ncf1 gene in the rat (2) and in the
mouse (3). The Ncf1 protein is a part of the NADPH
MRC Human Immunology Unit and Department of oxidasecomplexmediatingoxidativeburst.Thediscovery
Clinical Neurology, Weatherall Institute of Molecular oftheNcf1polymorphismledtoanewproposedpathway
Medicine, John Radcliffe Hospital, University of Oxford, inwhichoxygenradicalsmodifyantigenpresentationand
UK theresultingactivationofautoreactiveTcells.Micewith
thedeficientNcf1allelearemoresusceptibletoCIA,and
There is strong evidence that autoimmunity to myelin also developed a chronic form of arthritis. Interestingly,
antigens plays a major role in the development of the immune response to CII was enhanced by the Ncf1
multiple sclerosis. Several myelin-derived autoantigenic deficiency linking the Ncf1 pathway to the adaptive
targets have been described and include myelin basic immune response. Oxidation of T cell membranes seem
protein(MBP),proteolipidproteinandmyelinoligoden- to be a key event in the pathogenic mechanism as
drocyte glycoprotein. There has been a particular focus reduction of T cell membranes induces arthritis in rats
onMBPforatleasttworeasons:MBP-specificCD4+T- (4). On the basisof these findings anew type oftherapy
cell receptors (TCRs) have been found in multiple
S344 Sunday 17 June 2007 Inflamm.Res., Supplement 3 (2007)
has been developed based on agents activating the S01.3
NADPH oxidase complex (5).
References MYASTHENIA GRAVIS
1. Brunsberg et al Eur J Immunol; 1994.
2. Olofsson et al. Nat Genet; 2003. Angela Vincent
3. Hultqvist et al. Proc Natl Acad Sci USA. 2004.
4. Gelderman et al.. Proc Natl AcadSci USA, 2006. Honorary Consultant inImmunology, Neurosciences
5. Hultqvist M, et al. PLoS Medicine, 2006. Group, Weatherall Institute of Molecular Medicine,
Department of Clinical Neurology, Oxford,UK
Contactinformation:DrRikardHolmdahl,LundMedical
InflammationResearch, Lund University, Lund, Sweden Myasthenia gravis is a prototypic autoimmune disease,
E-mail: [email protected] caused in most cases by autoantibodies to the muscle
acetylcholine receptor (AChR) at the neuromuscular
junction. The antibodies reduce the number of AChR
S01.2 leading to failure of neuromuscular transmission and
muscle weakness. The AChR antibodies as measured in
ENU MUTAGENESIS: UNPICKING THE IMMUNE conventional immunoprecipitation assays are IgG, high
SYSTEM affinity, polyclonal and specific for human AChR. They
reduce the numbers of AChR by antigenic modulation
RichardCornall and by complement-mediated damage to the neuromus-
cular junction.
Nuffield Department of Clinical Medicine, University of
Oxford,JohnRadcliffeHospital,Headington,Oxford,UK Myastheniagravis has a veryintriguingrelationshipwith
thethymusgland.Inmanyyoungerpatients,thethymusis
ENU mutagenesis: unpicking the immune system. hyperplastic with immune cell infiltrates and germinal
Animals with targeted or spontaneous mutations have centreformation.Aroundthegerminalcentres,withinthe
beenthecornerstonesofmostofthenoveldiscoveriesin medulla, there are rare muscle-like cells called myoid
adaptive immunity over the last 20 years. . Much of our cells that express AChRs. There are many B cells and
understanding of the immune system rests upon mouse plasmacellsandthymiclymphocytepreparationssynthe-
mutantsorvariantsandrarehumandisorders,whichhave sise AChR antibodies. The possibility that the thymic
been essential entry points into some of the most AChRinducesthegerminalcentreformationandAChR
importantmechanisms of immune antibodysynthesis is supported by much evidence. Some
patients, however, have thymic tumours and in these the
regulation: for example, H2-restriction and the Ir gene role of the thymus is less clear.Moreover,older patients
effect, fas/ gld (cell death), scurfy/IPEX (T-regs), nude/ withtypicalmyastheniausuallyhavethymictissuewhich
DiGeorge syndrome (thymus), aire/APECED (negative is normal for their age.
selection),androquin(germinalcentres).Thesepathways
are conserved between mouse and man, and therefore There are up to 20% of myasthenia patients that do not
access to the human and mouse genome sequence now have the typical AChR antibodies. Some of these have
makesitpossibletoacceleratethediscoveryprocessata instead antibodies to muscle specific kinase, a receptor
rate not previously possible. Until recently the rarity of tyrosine kinase that is restricted to the neuromuscular
new genetic variants with phenotypes affecting immune junction. The pathogenic mechanisms by which the
responses to antigens has been a limiting factor in the antibodies cause disease are not yet clearly identified
discoveryofnewpathways.Toaddressthis,wehaveused and the evidence will be discussed.
ENU mutagenesis to accelerate the rate of single
nucleotidesubstitutionsinmicewithscreensforheritable Finally, among the patients who have neither AChR nor
defects in immune regulation. The mutant strains identi- MuSK antibodies by conventional testing, we have
fiedinthiswaycanthenbecomeentrypointsintofurther evidence for lower affinity antibodies to AChR which
pathways and mechanisms. can now be detected using molecular approaches which
will be described.
Contact information: Professor RichardCornall, Henry
Wellcome Building for Molecular Physiology, Wellcome Contactinformation:ProfessorAngelaVincent,Honorary
Trust Centre for Human Genetics, OxfordUniversity, Consultant inImmunology
Oxford,UK Neurosciences Group, Weatherall Institute of Molecular
E-mail: [email protected] Medicine,DepartmentofClinicalNeurology,Oxford,UK
E-mail: [email protected]
Inflamm.Res., Supplement 3 (2007) Sunday 17 June 2007 S345
S02.1 ascending dose clinical study is further exploring the
pharmacokinetics, pharmacodynamics and tolerability of
THE ROLE OF IL-6 IN INFLAMMATORY ARRY-162monotherapy.Inaddition,wehaveinitiateda
DISEASE AND CANCER clinical trial designed to evaluate ARRY-162 in combi-
nation with methotrexate in patients with rheumatoid
Ashlyn Eaton Bassiri arthritis.
CentocorResearchandDevelopmentInc.,IDepartmentof Contact information: Dr Kevin Koch, ArrayBiopharma
Immunobiology,Radnor, PA, USA Inc.Boulder, CO, USA
E-mail: [email protected]
Abstract not available at the time of printing.
Contact information: Dr Ashlyn Eaton Bassiri, Centocor S02.3
Research and Development Inc., IDepartmentof
Immunobiology, Radnor, PA, USA ROCK-2 SELECTIVE INHIBITORS FOR THE
TREATMENT OF ONCOLOGY AND FIBROTIC
DISEASE
S02.2
James Ellis(1), E Kim(1), SMcGonigle(1), O
THE EFFECTS OF MEK INHIBITORS IN Schueller(1), J Ferkany(1), B Humphreys(2), P
CANCER AND INFLAMMATION Sweetnam(1)
Kevin Koch (1) Surface Logix, Brighton,MA, USA
(2) Renal Division,Department of Medicine, Brigham &
ArrayBioPharma, Boulder, Co, USA Women:s Hospital, Boston, MA, USA
The MEK-ERK pathway is a central signal transduction Rhokinases(ROCK)areinvolvedinmanyphysiological
pathway, used in normal cells, in cancer cells, and in and pathological processes including smooth muscle
inflammatorydiseases.Incancer,MEKisdown-streamof contraction, cytoskeletal arrangement, cell adhesion,
Ras and Raf, two molecules often mutated in many migration and proliferation.ROCKHs prominent role in
cancers. MEK is activated in numerous inflammatory cytoskeletal architecture suggests that ROCK inhibitors
conditions, including rheumatoid arthritis, IBD and should have therapeutic impact in oncology and fibrotic
COPD. We have developed two potent, selective, ATP- diseases which require cytoskeletal rearrangement to
uncompetitive, MEK1/2 inhibitors and have used these progress.Wehavesynthesizedsmallmoleculeinhibitorsof
inhibitorstoexploretherolesofMEK1/2incancerandin ROCKwhicharespecificfortheROCK-2isoform.These
inflammatory diseases. ROCK-2 inhibitors, typified by SLx-2119 and SLx-3060,
arepotent(IC50<100nM),selectiveforROCK-2(>100
ARRY-886 (AZD6244) is an inhibitor of MEK1/2 fold selectivity for ROCK-2 over ROCK-1) and exhibit
currentlyindevelopmentforcancer.Phase1determined good oral bioavailability.This talk will focus on several
theMSD(100mg)andthesafetyofthecompoundgiven areasinoncologyandfibroticdiseasewheretheabilityto
continuously. In decreasing frequency, common treat- demonstrate an in vitro effect on the cytoskeleton
ment-related side effects were rash, diarrhea, nausea, translates into activity in the disease model in vivo.SLX-
peripheral edema, and vomiting. Paired pre- and post- 2119 inhibits cell proliferation and migration in several
dosetumorbiopsiesshowedareductioninpERK(-83%) tumor cell lines including HT-1080, PANC-1 and MDA-
and proliferative index (-46%). The trough plasma MB-231.Moreoverinxenograftstudiesusingnudemice,
concentration (400 ng/ml) corresponded to ~40% inhib- SLx-2119significantly inhibited tumor growth with these
itionofpERK.About45%ofptshadstablediseaseafter same cell lines. In liver fibrosis, SLx-2119 prevents the
2 months. These results demonstrate that ARRY-886 differentiation of rat primary hepatic stellate cells into
(AZD6244)iswell-tolerated,hitsitstarget,andproduces myofibroblasts and inhibits the proliferation of myofi-
a high incidence of long-lasting stable disease. There are broblasts as well as inhibiting hepatic steatosis in an
severalon-goingPhase2studies,inmelanoma,colorectal, atherosclerosis model.SLx-3060 is an effective anti-
lung and pancreatic cancer. fibroticagentinthekidneyunilateralurethralobstruction
model and inhibits renal fibroblast differentiation and
ARRY-162 is another potent, selective MEK 1/2 inhib- proliferation.These data suggest that ROCK-2 selective
itor,currently indevelopmentforinflammatorydiseases. inhibition of cytoskeletal modification in key cell types
When human whole blood was stimulated with TPA, (e.g. tumor cells, stellate cells and fibroblasts) by
ARRY-162inhibitedTNFa,IL-1bandIL-6(IC50sof23, compounds such asSLX-2119 and SLx-3060 will provide
21 and 21 nM, respectively). 50% inhibition of pERK effective treatment for oncology and fibrotic disease.
required 280 nM. ARRY-162 was highly efficacious in
CIA and AIA rat models, with ED50s of 3 and ~10 mg/ Contact information: Dr James Ellis, Surface Logix,
kg, respectively. In normal volunteers ARRY-162 was Department of Biology, Brighton, MA, USA
well-toleratedandtherewasadose-proportionalincrease E-mail: [email protected]
in drug exposure. In ex vivo blood samples, there was a
dramatictime-andconcentration-dependentinhibitionof
TPA-induced TNFa and IL1b. An on-going multiple
S346 Sunday 17 June 2007 Inflamm.Res., Supplement 3 (2007)
S02.4 laboratory findings, the IL-6 function in inflammation
could be analyzed for the induction of inflammatory
THE INTERSECTION OF CANCER AND molecules,suchasserumamyloidA(SAA).SAAmRNA
INFLAMMATION: EVIDENCE FOR THE ROLE induction, SAA promoter activity and assembling of
OF COX-2 transcriptional factors on SAA promoter were analyzed
bytherealtimeRT-PCR,gelshiftassayandDNAaffinity
Andrew J Dannenberg chromatography in hepatocyte stimulated with the pro-
inflammatory cytokines, IL-6, IL-1 and TNF-alpha. In
Weill Medical College of Cornell University result, IL-6 was an essential cytokine in induction of
SAAmRNA through the activation of STAT3 which
Cyclooxygenases (COX) catalyze the first step in the constructed the complex with NF-kappaB p65 and a co-
synthesis of prostaglandins (PG) from arachidonic factor P300. Although there was no STAT3 consensus
acid.COX-1 is constitutively expressed.The COX-2 gene region on SAA promoter, STAT3 bound at the 3 site of
is an immediate early-response gene that is induced by NF-kappaB RE. The above research proved that IL-6
variety of mitogenic and inflammatory stimuli.Levels of signalisessentialonthesynergisticinductionofSAAvia
COX-2 are increased in both inflamed and malignant newly discovered STAT3 transcriptional mechanism,
tissues.In inflamed tissues, there is both pharmacological suggesting the presence of this STAT3 mechanism in
and genetic evidence that targeting COX-2 can either inflammation,andconfirmingthenormalizationofserum
improve (e.g., osteoarthritis) or exacerbate symptoms SAA level by IL-6 blocking therapy in inflammatory
(e.g., inflammatory bowel disease).Multiple lines of diseases. This research method develops a subsequent
evidence suggest that COX-2 plays a significant role in therapyforseriousAAamyloidosisbyinhibitionofSAA
carcinogenesis.The most specific data that support a production, and elucidates the cytokine mechanism on
cause-and effect relationship between COX-2 and immunopathogenesis of chronic inflammatory diseases.
tumorigenesis come from genetic studies.Overexpression
of COX-2 has been observed to drive tumor formation Contact information: Professor Kazuyuki Yoshizaki,
whereasCOX-2deficiencyprotectsagainstseveraltumor Osaka University, HealthCare Center, Osaka, Japan
types.Selective COX-2 inhibitors protect against the E-mail: [email protected]
formationandgrowthofexperimentaltumors.Moreover,
selective COX-2 inhibitors are active in preventing
colorectal adenomas in humans.Increased amounts of S03.2
COX-2-derived PGE2 are found in both inflamed and
neoplastic tissues.The fact that PGE2 can stimulate cell CHEMOKINES IN RENAL INJURY
proliferation, inhibit apoptosis and induce angiogenesis
fitswithevidencethatinductionofCOX-2contributesto TakashiWada(1), K Matsushima(2), S Kaneko(1)
bothwoundhealingandtumorgrowth.Takentogether,it
seems likely that COX-2inductioncontributes towound (1) Kanazawa University, Japan
healinginresponsetoinjurybutreducesthethresholdfor (2) University of Tokyo, Japan
carcinogenesis.
Accumulatingevidenceindicatesthatchemokine/chemo-
Contact information: Dr Andrew Dannenberg,Weill kinereceptorsystemplaysakeyroleinthepathogenesis
Medical College of Cornell University, Department of of various renal diseases via leukocyte migration. Path-
Medicine, New York, NY, USA ophysiologicalimpactsof chemokines have shed lighton
E-mail: [email protected] molecular mechanisms of leukocyte trafficking and their
activation in the inflammatory aspects of progressive
renal injury.Locally expressed chemokines are proven to
S03.1 be capable of inciting leukocyte migration to the kidney,
resulting in initiating and promoting chronic kidney
EFFICACY AND PATHOGENIC ANALYSIS OF diseases.The possible positive amplification loop from
CHRONIC INFLAMMATORY DISEASES BY THE CXC chemokines to CC chemokines may contribute to
IL-6 BLOCKING THERAPY progressiverenalinjury,resultinginsclerosis/fibrosis.Itis
ofnotethatmonocytechemoattractantprotein(MCP)-1/
KazuyukiYoshizaki(1),KHagihara(2),TNishikawa(1),J monocyte chemotactic and activating factor (MCAF)/
Song(1), A Matsumura(2) CCL2, a prototype of CC chemokines, promotes and
escalates chronic kidney diseases with any etiologies via
(1) Health Care Center, Osaka University, Japan theinfiltrationandactivationofmonocytes/macrophages,
(2)OsakaUniversityGraduateSchoolofMedicine,Japan proteinuria and collagen synthesis.Interactions between
infiltrated inflammatory cells and resident renal cells
It is still less known about the actual pathogenic role of eventually lead to the progression of fibrosis. New
IL-6 inthe inflammatory status. Toknow the pathogenic insights into renal fibrosis have been uncovered by the
role of IL-6 and the efficacy of IL-6 blockade in regulationoffibrocytesdependentonchemokinesystem.
inflammation, a humanized anti-IL-6 receptor antibody, In addition, recent studies demonstrate that chemokines
Tocilizumab, was used for the treatment in chronic have been expanding their universe beyond leukocyte
inflammatory diseases, such as CastlemanHs disease, migration to the kidney, including homeostasis, develop-
rheumatoid arthritis and CrohnHs disease. Since IL-6 ment and repair of the kidney.The selective intervention
blockingtherapyimprovedtheclinicalsymptomsandthe of chemokines might have the therapeutic potential to