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Immunopharmacology of inflammation
Abstracts
627
IMMUNOPHARMACOLOGY OF INFLAMMATION
INTERLEUKIN C.J.
Dunn
I PROMOTES and
W.E.
LEUCOCYTE
Fleming,
ADHESION
UpJohn
Co.,
TO
ENDOTHELIAL
Kalamazoo,
CELLS
IN
VITRO.
15B
U.S.A.
Cultured human endothelial cells (ECS) exposed to interleukin I (IL-I) exhibited enhanced adhesiveness for human polymorphonuclear and mononuclear leukocytes. This phenomenon was dose-dependent. Contact between E C S a n d I L - I f o r at l e a s t 2 h o u r s w a s e s s e n t i a l for expression of increased adhesiveness. Incubation for shorter periods of t i m e d i d n o t induce significant changes in E C - l e u c o c y t e adhesion compared with cultures having received no IL-I. Thus IL-I may stimulate adhesion of l e u k o c y t e s to v e s s e l w a l l s v i a a d i r e c t e f f e c t o n E C S - t h e s a m e p h e n o m e n o n was not observed between leucocytes and other cell types, finally it w a s s h o w n to be a p r o t e i n synthesis dependent effect. Different factors were involved in v l v o .
EFFECT D.A.
OF
THERAPEUTIC
Willoughby, Dept. E x p . P a t h . ,
AGENTS
ON
IMMUNE
INFLAMMATION
& CARTILAGE
A. A i - D u a l J , F. d e B r l t o a n d A . D . S e d g w i c k St. B a r t h o l o m e w ' s Hospital Medical College,
DEGRADATI~
London,
16
UK
Rats sensitlsed to B . P e r t u s s i s had subcutaneous air pouches induced on their backs and were challenged at 14 d a y s i n t o t h e a i r p o u c h . This provoked a good inflammatory response persisting f o r up to 3 w e e k s . Nonsteroidal anti-lnflammatorles and dexamethasone reduced this response, whereas D-penlcillamlne and levamlsole either potentiated or had no significant effect. Eplphyseal cartilage implanted into either Immunologically inflamed air pouch or non-lnflamed showed no greater l o s s of proteogtycan. Similarly all the drug treatments showed proteotlon of cartilage. This demonstrates t h e l a c k of c o r r e l a t i o n between inflammation and cartilage degradation.
THE USE OF C Y C L O P H O S P H A M I D E AS A T O O L F O R I D E N T I F Y I N G AN I M M U N O L O G I C A L PATHWAY IN H A T S . F.B. De Brito and D.A. Willoughby Dept. Experimental Pathology, St. B a r t h o l o m e w ' s Hospital Medical College, London UK Rats treated with cyclophosphamlde (CYP; iOO mg/kg i.p.) 3 days before appropriate sensitisatlon f a l l to d e v e l o p adjuvant arthritis, collagen arthritis, experimental allergic encephalomyelitis or t h e d e l a y e d skin reaction ( D S H ) to e g g a l b u m i n / F r e u n d s incomplete adjuvant (OA/FIA) and become i m m u n e to s u b s e q u e n t induction by relnoculatlon. This acquired resistance appears specific as r a t s r e s p o n d n o r m a l l y to o x a z o l o n e and all but the OA/FIA sensitised rats can produce the OA/FIA DSH. However antiOA tltres and Artbus skin reactivity were normal in t h e l a t t e r i n d i c a t i n g recovery of t h e h u m e r a l l i m b of t h e i r i m m u n e s y s t e m . Since CYP pre-treat m e n t in t h e r a t d o e s n o t a f f e c t i n d u c t i o n of D S R to o x a z o l o n e , tuberculin or OA/FIA (Int.Arch. Allergy Appl. Immunol., 1984;73:92) thi~ data indicat~ that CYP sensitive delayed type hypersensitivity reactions in t h i s s p e c i e s are a distinct group that are not dependent on antibodies b u t to t h e i r susceptibility to t o l e r o g e n i c mechanisms.
17
627
IMMUNOPHARMACOLOGY OF INFLAMMATION
INTERLEUKIN C.J.
Dunn
I PROMOTES and
W.E.
LEUCOCYTE
Fleming,
ADHESION
UpJohn
Co.,
TO
ENDOTHELIAL
Kalamazoo,
CELLS
IN
VITRO.
15B
U.S.A.
Cultured human endothelial cells (ECS) exposed to interleukin I (IL-I) exhibited enhanced adhesiveness for human polymorphonuclear and mononuclear leukocytes. This phenomenon was dose-dependent. Contact between E C S a n d I L - I f o r at l e a s t 2 h o u r s w a s e s s e n t i a l for expression of increased adhesiveness. Incubation for shorter periods of t i m e d i d n o t induce significant changes in E C - l e u c o c y t e adhesion compared with cultures having received no IL-I. Thus IL-I may stimulate adhesion of l e u k o c y t e s to v e s s e l w a l l s v i a a d i r e c t e f f e c t o n E C S - t h e s a m e p h e n o m e n o n was not observed between leucocytes and other cell types, finally it w a s s h o w n to be a p r o t e i n synthesis dependent effect. Different factors were involved in v l v o .
EFFECT D.A.
OF
THERAPEUTIC
Willoughby, Dept. E x p . P a t h . ,
AGENTS
ON
IMMUNE
INFLAMMATION
& CARTILAGE
A. A i - D u a l J , F. d e B r l t o a n d A . D . S e d g w i c k St. B a r t h o l o m e w ' s Hospital Medical College,
DEGRADATI~
London,
16
UK
Rats sensitlsed to B . P e r t u s s i s had subcutaneous air pouches induced on their backs and were challenged at 14 d a y s i n t o t h e a i r p o u c h . This provoked a good inflammatory response persisting f o r up to 3 w e e k s . Nonsteroidal anti-lnflammatorles and dexamethasone reduced this response, whereas D-penlcillamlne and levamlsole either potentiated or had no significant effect. Eplphyseal cartilage implanted into either Immunologically inflamed air pouch or non-lnflamed showed no greater l o s s of proteogtycan. Similarly all the drug treatments showed proteotlon of cartilage. This demonstrates t h e l a c k of c o r r e l a t i o n between inflammation and cartilage degradation.
THE USE OF C Y C L O P H O S P H A M I D E AS A T O O L F O R I D E N T I F Y I N G AN I M M U N O L O G I C A L PATHWAY IN H A T S . F.B. De Brito and D.A. Willoughby Dept. Experimental Pathology, St. B a r t h o l o m e w ' s Hospital Medical College, London UK Rats treated with cyclophosphamlde (CYP; iOO mg/kg i.p.) 3 days before appropriate sensitisatlon f a l l to d e v e l o p adjuvant arthritis, collagen arthritis, experimental allergic encephalomyelitis or t h e d e l a y e d skin reaction ( D S H ) to e g g a l b u m i n / F r e u n d s incomplete adjuvant (OA/FIA) and become i m m u n e to s u b s e q u e n t induction by relnoculatlon. This acquired resistance appears specific as r a t s r e s p o n d n o r m a l l y to o x a z o l o n e and all but the OA/FIA sensitised rats can produce the OA/FIA DSH. However antiOA tltres and Artbus skin reactivity were normal in t h e l a t t e r i n d i c a t i n g recovery of t h e h u m e r a l l i m b of t h e i r i m m u n e s y s t e m . Since CYP pre-treat m e n t in t h e r a t d o e s n o t a f f e c t i n d u c t i o n of D S R to o x a z o l o n e , tuberculin or OA/FIA (Int.Arch. Allergy Appl. Immunol., 1984;73:92) thi~ data indicat~ that CYP sensitive delayed type hypersensitivity reactions in t h i s s p e c i e s are a distinct group that are not dependent on antibodies b u t to t h e i r susceptibility to t o l e r o g e n i c mechanisms.
17