Species differences in human and rat islet sensitivity to human cytokines. Monoclonal anti-interleukin-1 (IL-1) influences on direct and indirect IL-1-mediated islet effects.
Cytokine
; 3(2): 117-24, 1991 Mar.
Article
em En
| MEDLINE
| ID: mdl-1888882
ABSTRACT
Species differences in sensitivity to human recombinant cytokines were observed when human or rat islets were co-cultured with human recombinant cytokines for 6 days. Suppression of both human and rat islet insulin secretion resulted from co-culture with recombinant interleukin-1 alpha (rIL-1 alpha) or interleukin-1 beta (rIL-1 beta); however, direct rIL-1 alpha and rIL-1 beta cytotoxicity was seen with rat islets but not with human islets. Human islet insulin secretion was also suppressed during co-culture with recombinant tumor necrosis factor (rTNF) or interferon (rIFN), but not with lymphotoxin (rLT) or rIL-6; rat islet insulin secretion was not suppressed by any of these cytokines. No direct cytotoxic effects resulted from co-culture of human islets with rLT, rTNF, rIFN, or rIL-6; rLT was slightly cytotoxic for rat islets. Human islet cytotoxic synergy occurred between rLT and rIL-1 alpha, rIL-1 beta, or rIFN; synergy in suppression of human islet insulin secretion occurred between rLT and rIL-1 beta, and between rIFN and rTNF. Pretreatment of rIL-1 with monoclonal antibody (mAb) specific for non-crossreactive epitopes on rIL-1 alpha (H43 and H12) or rIL-1 beta (H34 and H21) prevented islet cytotoxic synergy between rIL-1 alpha or rIL-1 beta, respectively, and rLT. Although all four mAb's neutralize the thymocyte and fibroblast stimulatory activities of rIL-1 alpha or rIL-1 beta, mAb H21 does not neutralize rIL-1 beta activity against rat islets. Implications for cytokine-mediated islet cytotoxicity and suppression of insulin secretion are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Ilhotas Pancreáticas
/
Interleucina-1
/
Insulina
/
Anticorpos Monoclonais
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cytokine
Ano de publicação:
1991
Tipo de documento:
Article