Elevated levels of prostaglandins D2, E2 and F2∝ in suction blister fluid from psoriatic lesions as compared with levels in uninvolved and clinically normal skin

352

63

MINI-PIG SKIN AS A POTENTIAL ALTERNATIVE REACTIONS. C.Hensby, L.Juhlin, **A.Fourtanier.

A.Chatelus,

A.Civier,

FOR PREDICTING HUMAN SKIN PHARMACOLOGICAL H.Schaefer,

*M.W.Greaves,

CIRD, Sophia Antipolis, France. **Institute of Dermatology, toire de Recherche, L'Or@al, Aulnay Sous Bois, France.

*A.K.BIack,

London, England.

*R.B~Lrr,

***Labors-

We have evaluated the mini-pig skin responsiveness to three different stimuli, namely Trafuril, UV-B a n d Anthralin, in an attempt to find a viable alternative animal model to reflect human skin inflammation and pharmacological responsiveness. Prostaglandins D2, E), F) and 6-oxo-PGF.~ were measured in suction blister fluid (by quantitative GC-MS3 from 5oth human andlmini-pigs. An example of the results obtained is outlined in the table for PGF Essentially similar quantitative results were obtained in both human 2w " and mini-piE skin, supporting the concept that this animal may accurately predict human skin inflammatory responsiveness. Control 5% Trafuril 24 h UV-B (PGF~, nEml mea~'~ SEM)

64

Human

18.2, . , 1.1 t n = a ° J

37.2, . ~ 4 . 0 ~n=A)

~ 32 4 2 [ 9 (n=13)

Mini-Pig

18.1, =i ~, 1.4 ~n z;

32.3, _, T 6.8 ~n=b;

30.7, . ~ 4.1 ~n--4)

:

TIME COURSE CHANGES IN LEVELS OF PROSTAGLANDINS, SKIN FOLLOWING INFRA-RED IRRADIATION.

D2 , E2 F2~ AND 6-oxo-PGFl~

C.N.Hensby, L.Juhlin, A.Civier, S.Shroot. Centre International de Recherches Dermatologiques,

Sophia Antipolis,

IN HUMAN

Valbonne,

France.

Previous time course studies for different types of ultraviolet irradiation (UVA, UVB and UVC) have revealed an elevation of various prostanoids at different times after irradiation. Me have now examined the time course of pharmacological effect of longer wavelength infra red irradiation on prostaElandln levels in human forearm skin. Frostsholds were extracted into ethyl acetate, purified by TLC and quantitated by GC-MS. All four prostanoids determined were elevated at 4.5 h after irradiation. Prostaglandlns D~ E~ and FTq continued to increase up to 18 h ~ after irradiation and then returned t~wa~ds n o d a l v a l u e s b e t w e e n 24 and 48 h o u r s . The c o n c e n t r a t i o n s o f 6 - o x o - P G ~ w , however, declined after 4.5 h su~esting a different site of synthesis, within skin, for this prostanoid, possibly the vaaculature. 63

ELEVATED LEVELS OF PROSTAGLANDINS ~ , E2 AND F2N IN SUCTION BLISTER FLUID FROM PSORIATIC LESIONS AS COMPARED WITH LEVELS IN UNINVOLVED AND CLINICALLY NORMAL SKIN. C.Hensby, L . J u h l i n , Centre International *Dept. Dermatolo~,

A.Civier, W.Schalla, *B.Berne, *G.Michaelson, *C.Vahlquist. de R e c h e r c h e s D e r m a t o l o g i q u e s , S o p h i a A n t i p o l i s , Valbonne, France. U n i v e r s i t y o f U p p s a l a , Sweden.

A variety of inflammatory stimuli (Trafuril, UV-B) have been shown t o i n c r e a s e t h e l e v e l s o f p r o s t a g l a n d i n s i n human s k i n . We now r e p o r t t h e e l e v a t i o n o f t h r e e p r o s t a n o t d s , PGE2, PGD2and PGF2q i n c h r o n i c i n f l a m m a t i o n o f human s k i n , as e x e m p l i f i e d by v a r i o u s typds of psoriatic lesions. Suction blisters raised on psoriatic lesions and normal appearing skin. The exudates following extraction were purified by TLC, and quantitated by stable isotope dilution GC-~¢S. Healthy Volunteers Psoriatic Uninvolved Psoriatic Lesions (n = 19) (n : 12) (n = i0) PGE 2 13.0 17.1 68.6 *** I.I ~P 3.5 "4" 5.9+++ PGF2 ~ 12.7 13.2 45.9*** 0.6 "1"0.7 _~ 3.2÷++ * * * = p(O.O01 r e l a t i v e t o h e a l t h y v o l u n t e e r s . +++ = p(O.O01 r e l a t i v e to pso. uninvolved.