Inhibition of Inducible Nitric Oxide Synthase Enhances Anti-tumour Immune Responses in Rats Immunized with IFN-gamma-Secreting Glioma Cells.
Badn, Wiaam LU ; Hegardt, Pontus LU ; Agemark, Maria LU ; Darabi, Anna LU ; Esbjörnsson, Magnus LU ; Smith, K E ; Janelidze, Shorena LU ; Salford, Leif LU ; Visse, Edward LU and Siesjö, Peter LU
(2007)
In Scandinavian Journal of Immunology
65(3).
p.289-297
- Abstract
- Interferon gamma (IFN-gamma) has successfully been used in immunotherapy of different experimental tumours. Mechanistically, IFN-gamma has extensive effects on the immune system including release of nitric oxide (NO) by upregulation of the inducible nitric oxide synthase (iNOS). NO has putative immunosuppressive effects but could also play a role in killing of tumour cells. Therefore, the aim of the present study was to clarify whether inhibition of iNOS in rats immunized with glioma cells (N32) producing IFN-gamma (N32-IFN-gamma), could enhance the anti-tumour immune response. Initially, both a selective iNOS, L-N-6-(I-Iminoethyl)-L-lysine (L-NIL), and non-selective, N-nitro-L-arginine methyl ester (L-NAME), inhibitor of NOS were tested... (More)
- Interferon gamma (IFN-gamma) has successfully been used in immunotherapy of different experimental tumours. Mechanistically, IFN-gamma has extensive effects on the immune system including release of nitric oxide (NO) by upregulation of the inducible nitric oxide synthase (iNOS). NO has putative immunosuppressive effects but could also play a role in killing of tumour cells. Therefore, the aim of the present study was to clarify whether inhibition of iNOS in rats immunized with glioma cells (N32) producing IFN-gamma (N32-IFN-gamma), could enhance the anti-tumour immune response. Initially, both a selective iNOS, L-N-6-(I-Iminoethyl)-L-lysine (L-NIL), and non-selective, N-nitro-L-arginine methyl ester (L-NAME), inhibitor of NOS were tested in vitro. After polyclonal stimulation with LPS and SEA, both L-NIL and L-NAME enhanced proliferation and production of IFN-gamma from activated rat splenocytes and this effect was inversely correlated to the production of NO. However, L-NIL had a broader window of efficacy and a lower minimal effective dose. When rats were immunized with N32-IFN-gamma), and administered NOS inhibitors by intraperitoneal (i.p.) mini-osmotic pumps, only splenocytes of rats treated with L-NIL, but not L-NAME, displayed an enhanced proliferation and production of IFN-gamma when re-stimulated with N32 tumour cells. Based on these findings, L-NIL was administered concurrently with N32-IFN-gamma cells to rats with intracerebral (i.c.) tumours resulting in a prolonged survival. These results show that inhibition of iNOS can enhance an IFN-gamma-based immunotherapy of experimental i.c. tumours implying that NO released after immunization has mainly immunosuppressive net effects. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/165581
- author
- Badn, Wiaam
LU
; Hegardt, Pontus
LU
; Agemark, Maria
LU
; Darabi, Anna
LU
; Esbjörnsson, Magnus
LU
; Smith, K E
; Janelidze, Shorena
LU
; Salford, Leif
LU
; Visse, Edward
LU
and Siesjö, Peter
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scandinavian Journal of Immunology
- volume
- 65
- issue
- 3
- pages
- 289 - 297
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000245080700010
- scopus:33847071929
- pmid:17309784
- ISSN
- 1365-3083
- DOI
- 10.1111/j.1365-3083.2007.01901.x
- language
- English
- LU publication?
- yes
- id
- d69832cf-69e9-4deb-baa3-d2004fb7da81 (old id 165581)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17309784&dopt=Abstract
- date added to LUP
- 2016-04-01 15:38:20
- date last changed
- 2022-01-28 06:21:59
@article{d69832cf-69e9-4deb-baa3-d2004fb7da81,
abstract = {{Interferon gamma (IFN-gamma) has successfully been used in immunotherapy of different experimental tumours. Mechanistically, IFN-gamma has extensive effects on the immune system including release of nitric oxide (NO) by upregulation of the inducible nitric oxide synthase (iNOS). NO has putative immunosuppressive effects but could also play a role in killing of tumour cells. Therefore, the aim of the present study was to clarify whether inhibition of iNOS in rats immunized with glioma cells (N32) producing IFN-gamma (N32-IFN-gamma), could enhance the anti-tumour immune response. Initially, both a selective iNOS, L-N-6-(I-Iminoethyl)-L-lysine (L-NIL), and non-selective, N-nitro-L-arginine methyl ester (L-NAME), inhibitor of NOS were tested in vitro. After polyclonal stimulation with LPS and SEA, both L-NIL and L-NAME enhanced proliferation and production of IFN-gamma from activated rat splenocytes and this effect was inversely correlated to the production of NO. However, L-NIL had a broader window of efficacy and a lower minimal effective dose. When rats were immunized with N32-IFN-gamma), and administered NOS inhibitors by intraperitoneal (i.p.) mini-osmotic pumps, only splenocytes of rats treated with L-NIL, but not L-NAME, displayed an enhanced proliferation and production of IFN-gamma when re-stimulated with N32 tumour cells. Based on these findings, L-NIL was administered concurrently with N32-IFN-gamma cells to rats with intracerebral (i.c.) tumours resulting in a prolonged survival. These results show that inhibition of iNOS can enhance an IFN-gamma-based immunotherapy of experimental i.c. tumours implying that NO released after immunization has mainly immunosuppressive net effects.}},
author = {{Badn, Wiaam and Hegardt, Pontus and Agemark, Maria and Darabi, Anna and Esbjörnsson, Magnus and Smith, K E and Janelidze, Shorena and Salford, Leif and Visse, Edward and Siesjö, Peter}},
issn = {{1365-3083}},
language = {{eng}},
number = {{3}},
pages = {{289--297}},
publisher = {{Wiley-Blackwell}},
series = {{Scandinavian Journal of Immunology}},
title = {{Inhibition of Inducible Nitric Oxide Synthase Enhances Anti-tumour Immune Responses in Rats Immunized with IFN-gamma-Secreting Glioma Cells.}},
url = {{http://dx.doi.org/10.1111/j.1365-3083.2007.01901.x}},
doi = {{10.1111/j.1365-3083.2007.01901.x}},
volume = {{65}},
year = {{2007}},
}