Journal article
Antidiabetogenic Effect of Pentoxifylline is Associated with Systemic and Target Tissue Modulation of Cytokines and Nitric Oxide Production
Journal of autoimmunity, Vol.16(1), pp.47-58
02/2001
DOI: 10.1006/jaut.2000.0456
PMID: 11221996
Abstract
We have shown recently that xanthine derivative pentoxifylline (PTX) downregulates an inflammatory autoimmune process triggered in genetically susceptible Dark Agouti rats by multiple low doses of streptozotocin (MLD-SZ, 20mg/kg/day ip for 5 days). We studied the cellular and molecular consequences of PTX treatment during MLD-SZ-induced diabetes with special emphasis on local vs. systemic production of inflammatory mediators. Administration of PTX (200mg/kg/day for 10 days) during induction of the disease reduced clinical signs of diabetes and protected rats from development of destructive intrainsulitis. Pentoxifylline did not affect diabetogenic effect of single high dose of SZ (100mg/kg SZ). Ex vivo analysis of the islets of Langerhans performed in early disease development revealed that PTX downregulates production of proinflammatory cytokines IFN-γ and TNF, as well as inducible nitric oxide synthase (iNOS) expression and NO production. In addition, PTX treatment suppressed splenocyte autoreactivity, as well as the frequency of cells expressing IL-2R and MHC class II antigens. There was no evidence of any changes in proportion of ICAM-1 and LFA-1 expressing splenocytes in comparison to control MLD-SZ-treated animals. In contrast to suppressed intraislet production, high peripheral expression of both iNOS mRNA and NO was found in MLD-SZ rats treated with PTX. Taken together, the data indicate that the effect on both systemic and intra-islet production of NO, suppression of autoreactive cell activation and of local type 1 cytokine release may contribute to the therapeutic benefit achieved by PTX in the rat.
Details
- Title: Subtitle
- Antidiabetogenic Effect of Pentoxifylline is Associated with Systemic and Target Tissue Modulation of Cytokines and Nitric Oxide Production
- Creators
- Stanislava Stošić-Grujičić - Institute for Biological Research ‘Siniša Stanković’ Belgrade, YugoslaviaDanijela Maksimović - Institute for Biological Research ‘Siniša Stanković’ Belgrade, YugoslaviaVladimir Badovinac - Institute for Biological Research ‘Siniša Stanković’ Belgrade, YugoslaviaTatjana Samardžić - Institute for Biological Research ‘Siniša Stanković’ Belgrade, YugoslaviaVladimir Trajković - Institute of Microbiology and Immunology, School of Medicine, Belgrade University, Belgrade, YugoslaviaMiodrag Lukić - Institute of Microbiology and Immunology, School of Medicine, Belgrade University, Belgrade, YugoslaviaMarija Mostarica Stojković - Institute of Microbiology and Immunology, School of Medicine, Belgrade University, Belgrade, Yugoslavia
- Resource Type
- Journal article
- Publication Details
- Journal of autoimmunity, Vol.16(1), pp.47-58
- Publisher
- Elsevier Ltd
- DOI
- 10.1006/jaut.2000.0456
- PMID
- 11221996
- ISSN
- 0896-8411
- eISSN
- 1095-9157
- Language
- English
- Date published
- 02/2001
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047729402771
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