In Vitro Effects of Oxpentifylline on Inflammatory Cytokine Release in Patients with Inflammatory Bowel Disease

Overview

Journal Gut

Specialty Gastroenterology

Date 1997 Apr 1

PMID 9176074

Citations 19

Authors

J M Reimund

S Dumont

C D Muller

J S KENNEY

M Kedinger

R Baumann

P Poindron

B Duclos

Affiliations

Soon will be listed here.

Abstract

Background: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of intestinal inflammation in inflammatory bowel disease.

Aim: To investigate the in vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with Crohn's disease and patients with ulcerative colitis.

Methods: PBMCs and mucosal biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 determined by enzyme linked immunosorbent assays (ELISAs).

Results: PTX inhibited the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in cultures from controls, patients with Crohn's disease, and those with ulcerative colitis. The concentrations of IL-6 and IL-8 were not significantly modified in PBMCs, but IL-6 increased slightly in organ culture supernatants.

Conclusions: PTX or more potent related compounds may represent a new family of cytokine inhibitors, potentially interesting for treatment of inflammatory bowel disease.

Citing Articles

The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.

Lugnier C Int J Mol Sci. 2022; 23(18).

PMID: 36142518 PMC: 9502408. DOI: 10.3390/ijms231810616.

Chitinases and Chitinase-Like Proteins as Therapeutic Targets in Inflammatory Diseases, with a Special Focus on Inflammatory Bowel Diseases.

Mazur M, Zielinska A, Grzybowski M, Olczak J, Fichna J Int J Mol Sci. 2021; 22(13).

PMID: 34203467 PMC: 8268069. DOI: 10.3390/ijms22136966.

Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease.

Qian X, Cai C, Li H, Lai L, Song D, Qiao Y Therap Adv Gastroenterol. 2019; 12:1756284819880733.

PMID: 31662792 PMC: 6796213. DOI: 10.1177/1756284819880733.

Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-α/NF-κB signaling pathways.

Qu R, Chen X, Hu J, Fu Y, Peng J, Li Y Sci Rep. 2019; 9(1):1348.

PMID: 30718736 PMC: 6362006. DOI: 10.1038/s41598-018-38174-2.

Inhibitory effects of pentoxifylline on inflammation-related tumorigenesis in rat colon.

Shirakami Y, Kochi T, Kubota M, Sakai H, Ibuka T, Yoshimi K Oncotarget. 2018; 9(74):33972-33981.

PMID: 30338039 PMC: 6188053. DOI: 10.18632/oncotarget.26119.

References

Schandene L, Vandenbussche P, Crusiaux A, Alegre M, Abramowicz D, Dupont E . Differential effects of pentoxifylline on the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells. Immunology. 1992; 76(1):30-4. PMC: 1421741. View

Mazlam M, Hodgson H . Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease. Gut. 1992; 33(6):773-8. PMC: 1379334. DOI: 10.1136/gut.33.6.773. View

Wardle T, Hall L, Turnberg L . Use of coculture of colonic mucosal biopsies to investigate the release of eicosanoids by inflamed and uninflamed mucosa from patients with inflammatory bowel disease. Gut. 1992; 33(12):1644-51. PMC: 1379576. DOI: 10.1136/gut.33.12.1644. View

Breese E, Braegger C, Corrigan C, Walker-Smith J, MacDonald T . Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa. Immunology. 1993; 78(1):127-31. PMC: 1421783. View

Ollivier V, Ternisien C, Vu T, Hakim J, de Prost D . Pentoxifylline inhibits the expression of tissue factor mRNA in endotoxin-activated human monocytes. FEBS Lett. 1993; 322(3):231-4. DOI: 10.1016/0014-5793(93)81576-l. View

Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C, Tytgat G . Tumour-necrosis-factor antibody treatment in Crohn's disease. Lancet. 1993; 342(8864):173-4. DOI: 10.1016/0140-6736(93)91375-v. View

Rott O, Cash E, Fleischer B . Phosphodiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1- but not type 2-associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats. Eur J Immunol. 1993; 23(8):1745-51. DOI: 10.1002/eji.1830230802. View

Reinecker H, Steffen M, Witthoeft T, Pflueger I, Schreiber S, Macdermott R . Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1993; 94(1):174-81. PMC: 1534387. DOI: 10.1111/j.1365-2249.1993.tb05997.x. View

Thanhauser A, Reiling N, Bohle A, Toellner K, Duchrow M, Scheel D . Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity. Immunology. 1993; 80(1):151-6. PMC: 1422099. View

10.

DeVault Jr G, Kohan D, Nelson E, Holman Jr J . The effects of oral pentoxifylline on the cytokine release syndrome during inductive OKT3. Transplantation. 1994; 57(4):532-40. View

11.

Mitsuyama K, Toyonaga A, Sasaki E, Watanabe K, Tateishi H, Nishiyama T . IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1994; 96(3):432-6. PMC: 1534558. DOI: 10.1111/j.1365-2249.1994.tb06047.x. View

12.

Ramani M, Khechai F, Ollivier V, Ternisien C, Bridey F, Hakim J . Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes. FEBS Lett. 1994; 356(1):86-8. DOI: 10.1016/0014-5793(94)01236-9. View

13.

Sher M, DAngelo A, Stein T, Bailey B, Burns G, Wise L . Cytokines in Crohn's colitis. Am J Surg. 1995; 169(1):133-6. DOI: 10.1016/s0002-9610(99)80121-4. View

14.

Neuner P, Klosner G, Schauer E, Pourmojib M, MacHeiner W, Grunwald C . Pentoxifylline in vivo down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha by human peripheral blood mononuclear cells. Immunology. 1994; 83(2):262-7. PMC: 1414954. View

15.

Peterson T, Isbrucker R, Hooper M . In vitro effect of platelet-derived growth factor on fibroproliferation and effect of cytokine antagonists. Immunopharmacology. 1994; 28(3):259-70. DOI: 10.1016/0162-3109(94)90061-2. View

16.

Bauditz J, Ruckert Y, Raedler A, Nikolaus S, Lochs H, Schreiber S . Tumour necrosis factor inhibition by oxpentifylline and intestinal inflammation in Crohn's disease. Lancet. 1995; 345(8962):1445. DOI: 10.1016/s0140-6736(95)92635-6. View

17.

Van Dullemen H, van Deventer S, Hommes D, Bijl H, Jansen J, Tytgat G . Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995; 109(1):129-35. DOI: 10.1016/0016-5085(95)90277-5. View

18.

Reimund J, Wittersheim C, Dumont S, Muller C, Baumann R, Poindron P . Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. J Clin Immunol. 1996; 16(3):144-50. DOI: 10.1007/BF01540912. View

19.

Reimund J, Wittersheim C, Dumont S, Muller C, KENNEY J, Baumann R . Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease. Gut. 1996; 39(5):684-9. PMC: 1383392. DOI: 10.1136/gut.39.5.684. View

20.

TRUELOVE S, Witts L . Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955; 2(4947):1041-8. PMC: 1981500. DOI: 10.1136/bmj.2.4947.1041. View