ESDR I JSID I SID Abstracts s191

1141 IJVA MAY INHIBIT UV-INDUCED IMMUNOSUPRESSION BY UPREGULATION

OF IL12 IN HUMAN KE.RATlNOCYI’ES. Seiii

Department of Dermatobgy, Sqom Medical University, Sapporn, Japan

Evidence is accumulating lo show that ultraviolet A (UVA) plays an augmentalive

or synergistic role with UVB on pathophysiobgkal conditions induced by solar

radiation, thus, UVA is carcinogenic and may play a mle in the development of skin

malignancies and in the induction of immunosuppression. However, it remains

unclear how UVA contributes to solar radiation-induced immune suppression.

Keratinocytes (KC) are known to produce cytokines which are a significant mediator

of inflammatory and immunobgic reactlmts in the skin exposed to solar radiation and,

thus, are thought lo be a significant mediator in the induction of immune suppression.

Much less attention has tbcused on the effects of solar UVA on the production of

KC-derived cytokines. To examine if UVA alters the expression and production of

cytokines from KC, SV40 txmsfomed human keratimcytes (SVHK) were cultured

and exposed to UVA at the dose range between 2.5 and 20 KJ/m*. Cimstitutive

expression of the p35 subunit of IL12 was detected by RT-FCR and the ~4.0 subunit

was induced by UVA irradiation dose-dependently. Considering that IL12 promotes

activation of Thl cells and prwenls the activation of Tb2 cells and, thus has hen

shown to block the induction of immune suppression in UV-irradiated animals, effect

of UVA on the expression of IL12 in KC suggests that WA may play an inhibitory

role in the solar radiation-induced immune suppression mediated by UVB.

1142 AUTOANTIBOD”3 TO C-REACTIVE PROTEIN AND OTHER ACUTE PHASE PROTEINS

IN SYSTEMIC AUTOIMMUNE DISEASES. Susanne

Meurerl, Department of Dermatology, Ludwig-Maximilians-University, Munich and

‘Deparmxent of Dermatology, University of Dresden, Germany

Autoantibodies lo C-reactive pmlein (CRP) were reported previously in palien& suffering

from toxic 01, syndrome. This syndrome resembles autoimmune diseases such as systemic

lupus erytbematosus or systemic sclemderma. We therefore examined the prevalence of

antibodies to CR? and other acute phase proteins in autoimmune diseases, includiig lupus

erythematosus, scleroderma, Primary biliary cirrhosis as well as in bone marrow

hansplantation-induced rhromc graft-versus-host disease and eosinaphilia-myalgia

Syndrome. I& antibodies lo CRP were found in 78 % of SLE and in 30% of SCLE patiena,

while patients with PBC were positive in 16% In patients with SSC predomtnamely IgG

antibodies to ce~loplasmtn in up to 45% were deleclable. Lack of systemic invo,vement like

in DLE and morphea correlated with low or absent antibody formation. Adsorption studies

revealed that “on native epitopes on the CRP mo,~u,e are the main target of antibodies.

Chronic inflammatory tissue injury in systemic autoimmune disease might increase the

presentation of cryptw ep~topes of CRP and other acute phase proteins to the threshold

required for T cell achvahon.

1143 LACK OF AN EFFECTIVE T CELL-MEDIATED IMMUNE ,RySE IN BASAL CELL CARCINOMAS: A POSSIBLE ROLE FOR IL-lo? Koov AJW ank 8’. ve” Heukelum A’, Vurevski VD=. van J,,oSt Th’. Prens EP’, Depth of Dermato-VenereoloQy’. PefhOlOQy’ and

tmmu”ologyJ, Erasmus University Ratterdam, The Netherlands.

Many tumors, including basal cell wrcinoma IBCCI have been observed fo escape

immune SurveillS”ce. Tumor “eStS of BCC are surrounded by vawinp deprees of inflam- matory infiltrate which mainly consists of actwated T cells. Despite the presence of these cells the T cell-mediated immune response is not effective. This may be caused by the tack of expression of molecules required for T cell-tumor cell interactions such as MHC cless I & ,I, ICAM-1, CD40 and CD80 187.1) on the tumor cells. I” addition to the absence of these molecules I” situ. the presence of immunosuppressive cytokines play a role in the lack of a” effective immune reSpo”se. The aim of our Study was to investigate the induction/upreQulation of HLA-DR. HLA-ABC, ICAM-I, CD40 and CD80 in BCC biopsies in e culture System UsinQ rHulFN-v. The levels of IL-10 were determined in the cubure media after culturing. The results Showed a hiQ”lflCe”t upregulation of ICAM- on the BCC cells and on the overlying epidermis after Stimulation with rHulFN-v. Expression of CO40 was sliphtly increased on tie BCC cells end Sig”ifice”tly upreputated on the overtying epidermis. No induction of HLA-DR and

CD80 was observed on the tumor cells, alfhouQh a stiphf increase was observed in the overlying epidermis. The levels of IL-10 detected in lbe culture Super”ete”fS of BCC b,ops,eS were SiQ”ifice”tty higher the” those in the c”lf”re s”pemete”fs of normal Ski” biopsies from BCC patients. A significant down-regulation of IL-1 0 levels was observed after &U”“Q titb rHUlFN-v. It me” be concluded the, BCC cells are, in this s”stem, “et able te ewress sufficient levels of malecules required for a” effective T cell-medmted immune response which may be caused by the presence of high levels of IL-10.

1144 CUTANEOUS CYTOKINE PRODUCI’ION FROM INITIAL OXAZOLONE

EXPOSURE Don E. Griswold and Edward F. Webb, Department of

Immunophammcology, SmithKline Beecham Pharmaceuticals. King of Prussia, PA,

USA

The production of cytokines in mouse skin exposed to oxazolone was measured and

compared to skin exposed to phorbol ester (PMA). Balblc mice were exposed to a

sensitizing dose of oxazolone on the left ear. The ear tissue was sampled at days O-7

following exposure. Tissue homogenates were analyzed by ELISA for the presence

of interferon gamma (IF?-y), interleukin-4 (IL-4), tumor necrosis factor (TN&) and

interleukin-2 (IL-2). The results indicated that IL-4 was maximal on day 3 (61.6

pg/ml), IL-2 was maximal on day 6 (37.8 pg/mI) and IF?-y was maximal on day 6

(64.3 pg/ml). No TNFa was detected. Subsequent exposure to ant,gen challenge on

day 7 gave nsf to higher levels of IM-y. TNFa and IL-2 measured 8 brs post

challenge (544 pg/ml of IF?-y, 152.9 pg/mI of TNFa and 120.5 pg/ml of IL-2) but

similar leves of IL-4 (67.8 pg/ml). In contrast, the irritative response to PMA

revealed only TNFa (161.7 pg/ml). Challenge of animals sensitned at a remote we

generated IFN-y and IL-2 but no measureable levels of IL-4 or TNFa. Taken

together, these results suggest that oxazolone sensitized and challenged skin is

hyperrespasive to antigen and that the irritative response to PMA does not include

INF-y, U-4 or IL-2 production.

1145

1146 PLATELET-SECRETED CYTOKINE RANTES IS INCREASED IN THE PLASMA,

AND SKIN LESIONS FROM HALF OF THE SEVERE ATOPIC DERMATITIS

PATIENTS. Yukie Niwa Institute for Immunology, Tosashbnizu, Japan.

Platelet-released cytokinc, RANTES levels were assessed in the plasma and skin

lesioos of more than two hundred patients with sevcm, moderate and mild atopic

dermatitis (AD), simultaneously with IFN-gamma, and IL 2,4, 5 and 10. A marked

increase in plasma RANTES levels and decrease in IL 10 were found in half of the severe

AD but not in moderate DI mild AD patients, however, an increase in IL 10 was found in

other AD patients. IgE, eosinophils and plasma IFN-gamma, IL 2 and IL 5 were

elevated in rank order of severe, moderate and mild AD group. Ski” RANTES levels

were slightly elevated in severe AD patients, while twelve extra-severe AD patients who

had ken resistant to corticoid ointment showed a marked increase in skin RANTES

levels. However, all of these twelve patients did not show an marked increase in plasma

RANTES levels nor a decrease in IL 10. Present study suggests that RANTES cytokme

seems to play some important role in the exaccrhation of AD, and Th, cell-suppressing

action by a decrease in IL10 may be mediated through RANTES. At foal extreme

worsened stages, RANTES may intiltrate into skin lesions from the blood.