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The use of cyclophosphamide as a tool for identifying an immunological pathway in rats
411
LATE ABSTRACTS INTERLEUKIN C.J.
Dunn
I PROMOTES and
W.E.
LEUCOCYTE
Fleming,
ADHESION
Upjohn
Co.,
TO
ENDOTHELIAL
Kalamazoo,
CELLS
IN
VITRO.
]5
U.S.A.
Cultured human endothelial cells (ECS) exposed to i n t e r l e u k i n I (IL-I) exhibited enhanced adhesiveness for human polymorphonuclear and mononuclear leukocytes. This phenomenon was dose-dependent. Contact between ECS and IL-1 for at least 2 hours was essential for expression of increased adhesiveness. Incubation for shorter periods of time did not induce significant changes in EC-leueocyte adhesion compared with cultures having received no IL-1. Thus IL-1 may stimulate adhesion of leukocytes to vessel walls via a direct effect on ECS the same phenomenon was not observed between leucocytes and other cell types, finally it was shown to be a protein synthesis dependent effect. Different factors were involved in vivo. -
EFFECT D.A. Dept.
OF
THERAPEUTIC
Willoughby, Exp.Path.
,
A. St.
AGENTS
ON
A1-Dualj, F. Bartholomew's
IMMUNE de
INFLAMMATION
Brito Hospital
and A.D. Medical
& CARTILAGE Sedgwiek College,
DEGRADATI~
London,
16
UK
Rats sensitised to B.Pertussis had subcutaneous air pouches induced on their backs and were challenged at 14 aays into the air pouch. This provoked a good inflammatory response persisting for up to 3 weeks. Nonsteroidal anti-inflammatories and dexamethasone reduced this response, whereas D-penicillamine and levamisole either potentiated or had no significant effect. Epiphyseal cartilage implanted into either immunologieally inflamed air pouch or non-inflamed showed no greater loss of proteoglycan. Similarly all the drug treatments showed protection of cartilage. This demonstrates the lack of correlation between inflammation and cartilage degradation. THE USE OF CYCLOPHOSPBAMIDE AS A T O O L F O R I D E N T I F Y I N G AN IMMUNOLOGICAL PATHWAY IN R 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 cyelophosphamide (CYP; lO0 mg/kg i.p.) 3 days before appropriate sensitisation fail to develop adjuvant arthritis, collagen arthritis, experimental allergic encephalomyelitis or the delayed skin reaction (DSR) to egg albumin/Freunds incomplete adjuvant (OA/FIA) and become immune to subsequent induction by reinoculation. This acquired resistance appears specific as rats respond normally to oxazolone and all but the OA/FIA sensitised rats can produce the OA/FIA DSR. However antiOA t i t r e s and Arthus skin reactivity were normal in the latter indicating recovery of the humoral limb of their immune system. Since CYP p r e - t r e a t ment in the rat does not affect induction of DSR to oxazolone, tuberculin or OA/FIA (Int.Areh. Allergy Appl. Immunol. , 1984;73:92) this data indicat~ that CYP sensitive delayed type hypersensitivity reactions in this species are a distinct group that are not dependent on antibodies but to their susceptibility to tolerogenic mechanisms.
~7
LATE ABSTRACTS INTERLEUKIN C.J.
Dunn
I PROMOTES and
W.E.
LEUCOCYTE
Fleming,
ADHESION
Upjohn
Co.,
TO
ENDOTHELIAL
Kalamazoo,
CELLS
IN
VITRO.
]5
U.S.A.
Cultured human endothelial cells (ECS) exposed to i n t e r l e u k i n I (IL-I) exhibited enhanced adhesiveness for human polymorphonuclear and mononuclear leukocytes. This phenomenon was dose-dependent. Contact between ECS and IL-1 for at least 2 hours was essential for expression of increased adhesiveness. Incubation for shorter periods of time did not induce significant changes in EC-leueocyte adhesion compared with cultures having received no IL-1. Thus IL-1 may stimulate adhesion of leukocytes to vessel walls via a direct effect on ECS the same phenomenon was not observed between leucocytes and other cell types, finally it was shown to be a protein synthesis dependent effect. Different factors were involved in vivo. -
EFFECT D.A. Dept.
OF
THERAPEUTIC
Willoughby, Exp.Path.
,
A. St.
AGENTS
ON
A1-Dualj, F. Bartholomew's
IMMUNE de
INFLAMMATION
Brito Hospital
and A.D. Medical
& CARTILAGE Sedgwiek College,
DEGRADATI~
London,
16
UK
Rats sensitised to B.Pertussis had subcutaneous air pouches induced on their backs and were challenged at 14 aays into the air pouch. This provoked a good inflammatory response persisting for up to 3 weeks. Nonsteroidal anti-inflammatories and dexamethasone reduced this response, whereas D-penicillamine and levamisole either potentiated or had no significant effect. Epiphyseal cartilage implanted into either immunologieally inflamed air pouch or non-inflamed showed no greater loss of proteoglycan. Similarly all the drug treatments showed protection of cartilage. This demonstrates the lack of correlation between inflammation and cartilage degradation. THE USE OF CYCLOPHOSPBAMIDE AS A T O O L F O R I D E N T I F Y I N G AN IMMUNOLOGICAL PATHWAY IN R 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 cyelophosphamide (CYP; lO0 mg/kg i.p.) 3 days before appropriate sensitisation fail to develop adjuvant arthritis, collagen arthritis, experimental allergic encephalomyelitis or the delayed skin reaction (DSR) to egg albumin/Freunds incomplete adjuvant (OA/FIA) and become immune to subsequent induction by reinoculation. This acquired resistance appears specific as rats respond normally to oxazolone and all but the OA/FIA sensitised rats can produce the OA/FIA DSR. However antiOA t i t r e s and Arthus skin reactivity were normal in the latter indicating recovery of the humoral limb of their immune system. Since CYP p r e - t r e a t ment in the rat does not affect induction of DSR to oxazolone, tuberculin or OA/FIA (Int.Areh. Allergy Appl. Immunol. , 1984;73:92) this data indicat~ that CYP sensitive delayed type hypersensitivity reactions in this species are a distinct group that are not dependent on antibodies but to their susceptibility to tolerogenic mechanisms.
~7