ImmunoTox Letter
Intestinal immunity-mediated allergy-Establishment ofEnglish pages

murine food allergy model l- (Tomoko Shindo et al., Food

Report of the 15th Annual Meeting of theJapanese Society of Immunotoxicology(JSIT2008)

and Drug Safety Center)
Immunomodulation by probiotic lactobacilli throughregulating functions of macrophages (Kan Sida, Yakult

Jun-ichi Sawada

Central Institute for Microbiological Research）(President of JSIT2008)

Mucosal immune dysfunction by the trichothecene
mycotoxins (James J. Pestka, Center for Integrative

The 15th Annual Meeting of the Japanese Society ofToxicology, Michigan State University) (Dr. Pestka

Immunotoxicology (JSIT2008) was held on September 11

participated as the exchange speaker from SOT ImToxand 12, 2008, at Tower Hall Funabori, Edogawa, TokyoSS.)(for details, see Annual Meeting of the JSIT english

Workshop: Secondary immunomodulatory effects andhomepage, http://www.immunotox.org/english/index.ht

allergenicity of pharmaceuticalsml). A total of 185 persons attended the meeting, and theRegulation of allergic immune response by PPAR agonists

meeting included 15 oral and 17 poster presentations in(Shigeharu Ueki, Akita University School of Medicine)addition to the special programs. I hope every attendee

The role of dopamine as an immune modulator (Kazuhisa

enjoyed JSIT2008. The titles of the special programs

Nakano, University of Occupational and Environmental

were as follows:

Health)Inter-laboratory validation studies on LLNA-DA andInvited Plenary Lecture: Immunotoxicology of innate

LLNA-BrdU (Hajime Kojima et al., National Institute ofimmunity (Stephen B. Pruett, College of Veterinary

Health Sciences)

Medicine, Mississippi State University, USA)

Validation of non-RI methods -Data analysis- (Takashi

Keynote Lecture :Omori and Takashi Sozu (Kyoto University School ofGenetic polymorphisms andmyelotoxicity of anti-cancer drugs (Jun-ichi Sawada,Public Health)National Institute of Health Sciences)

Briefing of ICCVAM LLNA peer review meeting

Master's Lecture:(Takahiko Yoshida, Asahikawa Medical College)

Immunotoxicogenomics ofenvironmental chemicals (Keiko Nohara, National
Institute for Environmental Studies)

The 16th Annual Meeting of theJapanese Society of Immunotoxicology

Symposium 1: Immunotoxicity of nanoparticles
Measures to evaluate the health effects of manufactured
nanomaterials (Akihiko Hirose, National Institute ofHealth Sciences）
The importance of characterization for nanoparticles
and its pulmonary effects in rats. (Akira Ogami et al.,
University of Occupational and Environmental Health）
Synergistic ef fects of nanoparticles/materials on
pathological conditions (Ken-ichiro Inoue et al., National
Institue for Environmental Studies)
Safety concerns of nanomaterials to skin: Safety and skinpenetration of nanomaterials (Kenji Sugibayasi, JoseiUniversity）
Symposium 2: Gut-associated lymphoid tissues and theirregulations
Regulation of gut immunity by retinoids (Makoto Iwata etAugust 27-28, 2009
Asahikawa Cultural Hall, Asahikawa, Japan
Theme: Children and Immunity
Invited Plenary Lecture I:Dori Germolec, PhD （NIEHS, USA）
Invited Plenary Lecture II:
Masao Kosuge (Director of Asahikawa Asahiyama Zoo)
Symposium: Children and Immunity
Workshop
Oral presentations / Poster presentations

President: Prof. Takahiko Yoshida
Secretary office: Dept. of Health Science, Asahikawa
Medical College, Asahikawa, Japan
Phone：0166-68-2402 FAX:0166-68-2409
E-mail：jsit16@asahikawa-med.ac.jp

al., Tokushima Bunri University）
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Vol. 13 No. 2 (2008)【Materials and Methods】

A prize for年 annual会 convention
賞

Excluding patients with history of cancer, rheumatoid

Elevation of aging-associated inflammatory
markers among atomic-bomb survivors

arthritis, chronic bronchitis, or myocardial infarction,

Tomonori Hayashi, Yoichiro Kusunoki, Yukari
Morishita, Hiroko Nagamura, Mayumi Maki,
Yoshiko Kubo, Kengo Yoshida, Kei Nakachi

AHS population, consisting of A-bomb survivors andDepartment of Radiobiology/Molecular Epidemiology,
Radiation Effects Research Foundation, Hiroshima, JAPAN[Abstract]
Among a cohort of Hiroshima atomic-bomb survivor, weobserved elevations of plasma inflammatory markers
such as IL-6, TNF- α , IL-10, CRP, ESR and total Igs aswell as ROS, in which exposure to 1 Gy of radiation wasestimated to correspond to about nine years of aging.
The results suggest that effects of radiation exposure
involve inflammatory response enhanced by accelerationof aging.

we randomly selected 442 study subjects from theunexposed controls. Plasma levels of infl ammatorymarkers (IL-6、TNF- α , CRP, IFN- γ , Igs) anderythrocyte sedimentation rate (ESR) were measured by
ELISA and the Westergren method, respectively.

【Results and Discussion】
Signifi cant elevations of the following infl ammatory
cytokines and markers were observed with increased
radiation dose: (1) Infl ammator y cytokines (IL-6,TNF- α , IFN- γ , and IL-10), (2) CRP, total ROS,and erythrocyte sedimentation rate (ESR), and (3)Immunoglobulin (Ig) levels. Also observed with increased
radiation dose was decreased percentage of CD4T cells.
Since both radiation exposure and aging were related toelevation of most of the inflammatory markers examined【Objective】
Even after more than 60 years have passed, exposure
to atomic-bomb radiation continues to have longterm health effects in survivors, whose risks of certain
inflammation-related diseases remain high. It has been
acknowledged in numerous reports that people exposed
to high-dose radiation in accidents or medical treatment
suffered from acute inflammatory reactions for several
days following exposure, although the long-term latein this study, we conducted our review by convertingradiation effects to an acceleration of aging. Namely,judging from IL-6, TNF- α , IL-10, CRP, total ROS,
ESR, and Ig, exposure to one Gy of atomic radiation was
found to correspond to a nine-year increase in aging.
These results suggest that atomic-bomb radiation might
have further accelerated inflammation status, which isordinarily promoted by the aging process.

effects of radiation on inflammatory status have yet tobe thoroughly clarified. We have learned much fromthe longstanding studies of atomic-bomb survivors,
who experienced the atomic bombings of Hiroshima andNagasaki in 1945. Two major cohort studies, the Life
Span Study (LSS) and the Adult Health Study (AHS),
have been conducted by RERF, of which the AHS is acomprehensive clinical follow-up study based on biennial
clinical examinations, for a selected subset of the LSSpopulation. In this study, we investigated association
between plasma levels of infl ammatory markers andROS, peripheral lymphocyte subsets, and radiationdose in Hiroshima A-bomb survivor subjects randomly
selected from the AHS population.
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throughout the world as insecticides in agriculture andA prize年
for encouragement
会 賞

eradicating agents for termites around homes. TheAssociations between HLA types andStevens-Johnson syndrome/ toxic
epidermal necrolysis in Japanese patients.

main toxicity of OPs is neurotoxicity, which is caused by

Saito Yoshiro1,2 , Tohkin Masahiro1,2 ,Kurose Kouichi1,2 , Sawada Jun-ichi1 ,Hasegawa Ryuichi1,2 , Sotozono Chie2 ,Kinoshita Shigeru2 , Takahashi Yukitoshi2,Furuya Hirokazu2 , Muramatsu Masaaki2,
Matsunaga Kayoko2 , Aihara Michiko2 ,Ikezawa Zenro2 , Kaniwa Nahoko1,2ylphosphonate, the by-products generated during sarin

12National Institute of Health Sciences , JSAR Research Groupthe inhibition of acetylcholinesterase. The author firstfound that diisopropylmethylphosphonate, diethylmeth
synthesis in the Tokyo sarin disaster, inhibited naturalkiller (NK) and cytotoxic T lymphocyte (CTL) activities,
then found that OPs significantly inhibited NK, CTL and
LAK activities both in vitro and in vivo. Furthermore,
the author found that OPs inhibit NK, CTL and LAKactivities by at least the following three mechanisms: 1)
OPs impair the granule exocytosis pathway of NK cells by
inhibiting the activity of granzymes, and by decreasing

Stevens-Johnson syndrome (SJS) and toxic epidermal

the intracellular level of perforin, granzymes andnecrolysis (TEN) are very rare, but severe cutaneousgranulysin; 2) OPs impair the FasL/Fas pathway of NK

adverse reactions induced by numerous drugs. Wecells; 3) OPs induce apoptosis of NK and T cells.

constr ucted a system to collect DNA samples ofSJS/TEN patients from all areas of Japan, and studied
associations between HLA types and SJS/TEN in

Contribution from overseas

Japanese. In the analysis of all 58 cases, HLA-DRB1*0901

Excellent Science and Outstanding
Hospitality: A Guest's view of the JSIT
meeting

was significantly associated with the occurrence ofSJS/TEN (corrected p value (Pc)<0.01), but its odds
ratio was rather small (odds ratio (OR)=2.38). In

Contributed by Stephen B. Pruett, PhD

the individual drug cases, HLA-B*5801 was strongly
associated with allopurinol-induced SJS/TEN (Pc=0.003;(Professor and Head, Department of Basic Sciences,OR=40.8). HLA-Cw*0302 , which was strongly linked

College of Veterinary Medicine, Mississippi State University, USA)with HLA-B*5801 , also showed a significant correlation(Pc=0.001, OR=127.9). We would like to continue

I was recently given the wonderful opportunity by

discovering genetic markers for SJS/TEN to avoid these

JSIT to visit Japan for the first time and to speak atsevere adverse reactions of drugs.

the JSIT meeting. I would like to express my thanks toDr. Sugita-Konishi for hosting Dr. Pestka and I at theNational Institute for Health Sciences and for showing
us some of the sights of Tokyo afterwards. In fact, theYoung power for immunotoxicological researchhospitality from everyone was exceptional and madethe entire experience very enjoyable. I am particularly

Mechanism of immunotoxicity oforganophosphorus pesticides

grateful to Kazuichi Nakamura, who spent almost 2 days

Qing Lishowing my wife and I some of the most interesting

Department of Hygiene and Public Health,places in the Tokyo area. I thoroughly enjoyed Japan.

Nippon Medical School, Tokyo, Japan

The people are friendly, the city is beautiful, there manye-mail: qing-li@nms.ac.jp

historical sites and parks, and the food is magnificent. I
was also very impressed with the subways and trains.

Abstract

In the area where I live, there is very little public

Organophosphorus pesticides (OPs) are widely usedtransportation, so an efficient system such as the one inTokyo was impressive to me.

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Vol. 13 No. 2 (2008)

Fig.1.Dr.Pruett

Fig.2.Tokyo Tower

I was very impressed with the meeting. My impression

JSIT and the Immunotoxicology Specialty Section (ISS) ofin comparing the Immunotoxicology Specialty Section

SOT to promote scientific interchange and cooperationof the Society of Toxicology with JSIT is that JSIT

between immunotoxicologists from Japan and the U.S. Dr.

may have even more interest and expertise in applied

Steve Pruett also participated this year as Past President

aspects of immunotoxicology than the Immunotoxicologyof the ISS-SOT to facilitate future exchanges between theSpecialty Section. I think the groups of researchersgroups.

in both organizations have interests that are nicelycomplementary as well as many common interests, soThis visit started upon our arrival in Tokyo on October

our decision to continue the exchange visits as a way to

8 where we were greeted by one of our hosts, Dr.

learn more about the work in both groups seems very

Kazuichi Nakamura of Shionogi and Co. Developmental

appropriate. I will be proposing to the Immunotoxicology

Research Laboratories, who familiarized us with theSpecialty Section Officers at the meeting in Baltimore

Tokyo area accommodations and plans for the meeting.

a standard procedure for our annual scientific exchange

The following day Dr. Yoshiko Sugita-Konishi, Director ofvisits, so JSIT leaders will know who will be arranging theDivision of Microbiology at NIHS hosted us at her agency

visit and when various parts of the process will occur. Ilaboratories. Both Dr. Pruett and I presented seminars towill also be able to tell our exchange visitors that they canan enthusiastic audience on our research related to stressexpect a thoroughly enjoyable visit.

and immunotoxicity. Following the seminars, we attended(Fig. 1 and 2)

a luncheon with scientists from the NIHS with extensive
follow-up discussions on our work and common researchinterests.

Participation at the 15th Annual
Meeting of the Japanese Society for
Immunotoxicology

In the afternoon, we met with Dr. Konishis labgroup and toured her outstanding facilities. Dr. Konishi

Contributed by Dr. James J. Pestka, PhD

studies microbial toxins and their effects on the immune(Professor, Department of Microbiology and Molecular Genetics,system. Later we visited with Dr. Jun-ichi Sawada who

Michigan State University, USA)is the current President of the JSIT. Dr. Sawada runs
an outstanding translational program linking humanI was given the wonderful opportunity to attend andgenetic polymorphisms and myelotoxicity of anti-cancer

Annual Meeting of the Japanesedrugs. The day ended in dinner with Dr. Konishi andSociety for Immunotoxicology (JSIT) in Tokyo during theDr. Masahiko Takino of Agilent Technologies where wesecond week of October. This visit was co-sponsored bydiscussed ongoing collaborative studies characterizing

present at the 15th─ 13 ─

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ImmunoTox Letter
Immunotoxic secondary metabolites produced by theby probiotic lactobacilli. The luncheon seminar was

black mold Stachybotrys.

presented by Dr. Mark Wing (Huntington Life Sciences,UK) on non-clinical strategies to mitigate the risk

On the following evening, the JSIT conference opening

for first-in-man studies with immunomodulator ydinner was held under Dr. Sawada s leadership where

dr ugs. Subsequent after noon sessions dealt with

we met with members of JSIT. Here we had further

immunotoxicogenomics and secondar y modulator y

discussions about future cooperation between JSIT andeffects and allergenicity of pharmaceuticals. I ended theISS-SOT. The following day the conference began withday by a solo visit to the Asakusa and Ginza areas which

the keynote lecture by Dr. Sawada and morning oral

represent some of the oldest and newest aspects of Tokyo,presentations. At the luncheon, Dr. Lawrence Jacob

respectively.

of Charles River Labs (UK) spoke on immunologicalassessment and use of biomarkers in translational

Ta k e n t o g e t h e r, t h i s w a s a n e n l i g h t e n i n g a n d

medicine. This was followed by a symposium on theinformative experience that enlarged my horizons on

immunotoxicity of nanoparticles and plenary address byimmunotoxicology research. Our Japanese hosts wereDr. Pruett on immunotoxicology and innate immunity.

warm and engaging- I am extremely grateful to Dr.

The second day began with oral presentations andNakamura, Dr. Sugita-Konishi and Dr. Sawada for theira symposium on gut associated lymphoid tissues

extraordinary kindness. The visit reminded me of why

and their regulations chaired by Dr. Reiko Teshima,

I entered this exciting field and also confirmed the fact

Division of Novel Foods and Immunochemistr y atthat scientists speak a universal language and continually

NIHS. Here I spoke on mucosal immune dysfunction bystrive for mutual improvement. I certainly encourage

the trichothecene mycotoxins. Other talks focused on

fellow ISS-SOT members to take the opportunity toregulation of gut immunity by retinoids, establishment

participate in the JSIT annual meeting in future years.

of a murine food allergy model, and immunomodulation(Fig. 3, 4)

Fig.3.Dr.Pestka

Fig.4.Senso-ji temple

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Currently in Korea, several hundred scientists may

Hope for Communication between
Japanese and Korean Immunotoxicologists

be involved with immunotoxicological research works.

Contributed by Dr.Yong Heo, DVM, PhD

But they are enrolled in major academic societies such

(Associate Professor, Department of Occupational Health,as society of immunology, toxicology, pharmacy, or other

Catholic University of Daegu, Korea)

health related organizations, therein we have no apparent
organization of immunotoxicology. One of lessons, which

Participation at 15th Annual Meeting of the Japanese

I got through participating JSIT annual meeting, is that

Society of Immunotoxicology gave me unforgettablescientists interested in immunotoxicology will be helpful

memory and many meaningful lessons. Even though iteach other nevertheless their major academic societies

was my first time to participate at JSIT annual meeting,

if we meet periodically and share or discuss important

I could see many familiar scientists whom I have met

issues or information on immunotoxicology. That s why, Iat Society of Toxicology annual meeting of the United

think, it is the time to seriously consider the organization

States.

of Korean society of immunotoxicology. If the KoreanFirst of all, it was so impressive to me that scientists

Society of Immunotoxicology comes to successfully

from many different scientific areas were gathering tolaunch, two societies can collaborate in future. Until

discuss hot issues of immuotoxicology and share valuable

then, I wish as many as Korean immunotoxicologists

information. Furthermore, no matter how different inparticipate JSIT meeting, and attempt to establish thetheir majors or workplaces, they were eager to work

harmonious relationship between two societies. For

together for up-grade of JSIT, in that scientists werethat reason, international symposium session would becoming from medical, pharmacy, or other life science

preferred at coming JSIT meeting.

academic organizations, national or private research
institute, and even many companies. It was also

Finally I would like to show my sincere gratitude to

noticeable to me that almost all participants were at theDr. Jun-ichi Sawada, president of JSIT, and Dr. Takahikoconference hall until closure of each day presentation,Yoshida, Dr. Keiko Nohara, and other JSIT staffs.

and discussions between speakers and floor participants

Because of their sacrificial efforts, 2008 JSIT came to bewere so active even though I could not completely

much more wonderful to all participants.

understand Japanese language.

(Fig. 5 and 6)

Fig.5.Dr.HeoFig.6.Dr.Heo with students

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