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Titolo:
INTERLEUKIN-12 PRIMES MACROPHAGES FOR NITRIC-OXIDE PRODUCTION IN-VIVOAND RESTORES DEPRESSED NITRIC-OXIDE PRODUCTION BY MACROPHAGES FROM TUMOR-BEARING MICE - IMPLICATIONS FOR THE ANTITUMOR-ACTIVITY OF INTERLEUKIN-12 AND OR INTERLEUKIN-2/
Autore:
WIGGINTON JM; KUHNS DB; BACK TC; BRUNDA MJ; WILTROUT RH; COX GW;
Indirizzi:
NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,INVIVO BIOTHERAPY SECT FREDERICK MD 21701 SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM FREDERICK MD 00000 SCI APPLICAT INT CORP,CLIN SERV PROGRAM FREDERICK MD 00000 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,DIV BASIC SCI FREDERICK MD 21701 HOFFMANN LA ROCHE INC,DEPT ONCOL NUTLEY NJ 07110
Titolo Testata:
Cancer research
fascicolo: 5, volume: 56, anno: 1996,
pagine: 1131 - 1136
SICI:
0008-5472(1996)56:5<1131:IPMFNP>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; L-ARGININE; ACTIVATED MACROPHAGES; MURINE MACROPHAGES; INTERFERON-GAMMA; TUMORICIDAL FUNCTION; EFFECTOR MECHANISM; NITROGEN-OXIDES; CYTO-TOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
60
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Wigginton et al., "INTERLEUKIN-12 PRIMES MACROPHAGES FOR NITRIC-OXIDE PRODUCTION IN-VIVOAND RESTORES DEPRESSED NITRIC-OXIDE PRODUCTION BY MACROPHAGES FROM TUMOR-BEARING MICE - IMPLICATIONS FOR THE ANTITUMOR-ACTIVITY OF INTERLEUKIN-12 AND OR INTERLEUKIN-2/", Cancer research, 56(5), 1996, pp. 1131-1136

Abstract

Interleukin-12 (IL-12) is a recently described immunoregulatory cytokine with potent therapeutic activity in various preclinical models of infectious or malignant disease, As part of our ongoing evaluation of potential mechanisms accounting for the potent antitumor activity of IL-12, we have investigated the influence of IL-12 administration on total serum nitrate/nitrite (NOx-) levels and the production of nitric oxide (NO) by peritoneal macrophages from normal and tumor-bearing mice. We report here that IL-12 administration to either normal or tumor-bearing mice for periods of time ranging from 7-19 days induced progressive increases in serum NOx- levels and primed peritoneal macrophages for NO production on subsequent exposure to lipopolysaccharide or IL-2ex vivo. Treatment of resident peritoneal macrophages of the macrophage cell line ANA-1 with IL-12 alone or IL-12 in combination with various other stimuli failed to induce NO production, suggesting that the effects of IL-12 occurred via an indirect mechanism. Furthermore, we have shown that not only was the production of NO by macrophages from untreated long-term, tumor-bearing mice suppressed compared with controlmice treated with vehicle or IL-12, but also that IL-12 administration overcame this suppression and delayed tumor growth. Lastly, we have shown that administration of weekly pulses of IL-2 in combination withIL-12 additively enhanced the priming of macrophages for NO production ex vivo and delayed tumor growth far more effectively than either agent alone. These observations and reports in the literature regarding the potential influence of NO on development of the immune response and on the regulation of tumor growth and vascularization suggest that NO may play a significant role in the antitumor activity of IL-12 and IL-2.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:36:49