Effect of Lignocaine on IL-6,IL-8,and MCP-1 in Peritoneal Macrophages and Endometriotic Stromal Cells

Abstract

Objective:

The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells.

Design:

Experimental in vitro study on human cells.

Population and Sample:

Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons.

Methods:

Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs.

Results:

The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls (P = .028 and P = .018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines (P = .043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment.

Conclusion:

Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.

Keywords

cytokine endometriosis gene expression lignocaine protein

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References

Giudice

Kao

. Endometriosis. Lancet. 2004;364(9447):1789–1799.

Houston

. Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev. 1984;6:167–191.

Olive

Schwartz

. Endometriosis. N Engl J Med. 1993;328(24):1759–1769.

Agic

Finas

Banz

Diedrich

Hornung

. Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest. 2006;62(3):139–147.

Yang

. Peritoneal cellular immunity and endometriosis. Am J Reprod Immunol. 1997;38(6):400–412.

Gazvani

Templeton

. Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction. 2002;123(2):217–226.

Haney

Muscato

Weinberg

. Peritoneal fluid cell populations in infertility patients. Fertil Steril. 1981;35(6):696–698.

. The role of cytokines in endometriosis. Am J Reprod Immunol. 2003;49(5):285–296.

Oral

Olive

Arici

. The peritoneal environment in endometriosis. Hum Reprod Update. 1996;2(5):385–398.

10.

McLaren

. Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update. 2000;6(1):45–55.

11.

Akoum

Lemay

Brunet

Hebert

. Cytokine-induced secretion of monocyte chemotactic protein-1 by human endometriotic cells in culture. The Groupe d’Investigation en Gynecologie. Am J Obstetr Gynecol. 1995;172(2 pt 1):594–600.

12.

Tseng

Ryan

Milam

Murai

Schriock

Landers

. Interleukin-6 secretion in vitro is up-regulated in ectopic and eutopic endometrial stromal cells from women with endometriosis. J Clin Endocrinol Metab. 1996;81(3):1118–1122.

13.

Berkkanoglu

Arici

. Immunology and endometriosis. Am J Reprod Immunol. 2003;50(1):48–59.

14.

Giudice

. Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine. Fertil Steril. 1994;61(1):1–17.

15.

Gazvani

Smith

Fowler

. Effect of interleukin-8 (IL-8), anti-IL-8, and IL-12 on endometrial cell survival in combined endometrial gland and stromal cell cultures derived from women with and without endometriosis. Fertil Steril. 2002;77(1):62–67.

16.

Rana

Braun

House

Gebel

Rotman

Dmowski

. Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis. Fertil Steril. 1996;65(5):925–930.

17.

Arici

Seli

Zeyneloglu

Senturk

Oral

Olive

. Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor. J Clin Endocrinol Metab. 1998;83(4):1201–1205.

18.

Arici

Oral

Attar

Tazuke

Olive

. Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells. Fertil Steril. 1997;67(6):1065–1072.

19.

Rier

Zarmakoupis

Becker

. Dysregulation of interleukin-6 responses in ectopic endometrial stromal cells: correlation with decreased soluble receptor levels in peritoneal fluid of women with endometriosis. J Clin Endocrinol Metab. 1995;80(4):1431–1437.

20.

Arici

Tazuke

Attar

Kliman

Olive

. Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells. Mol Hum Reprod. 1996;2(1):40–45.

21.

Hollmann

Durieux

. Local anesthetics and the inflammatory response: a new therapeutic indication? Anesthesiology. 2000;93(3):858–875.

22.

Cambridge

Parsons

Friend

Jones

. Some effects of lignocaine on cultured mouse peritoneal macrophages. Agents Actions. 1985;16(6):548–551.

23.

Cassuto

Sinclair

Bonderovic

. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand. 2006;50(3):265–282.

24.

Swanton

Shorten

. Anti-inflammatory effects of local anesthetic agents. Int Anesthesiol Clin. 2003;41(1):1–19.

25.

Lan

Harmon

Wang

Shorten

Redmond

. Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine. Anesth Analg. 2005;100(2):409–412.

26.

Lahav

Levite

Bassani

. Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells. Clin Exp Immunol. 2002;127(2):226–233.

27.

de Klaver

Buckingham

Rich

. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells. Anesth Analg. 2003;97(2):465–470.

28.

Bjorck

Dahlstrom

Ahlman

. Treatment of distal colitis with local anaesthetic agents. Pharm Toxicol. 2002;90(4):173–180.

29.

Edelstam

Sjosten

Salamon

. Pertubation with lignocaine—a possible new treatment for women with endometriosis and impaired fertility. Ups J Med Sci. 2001;106(1):51–57.

30.

Edelstam

Sjosten

Jablonowska

Kjellberg

Spira

. Pertubation with lidocaine—a non-hormonal, long-term treatment of dysmenorrhea due to endometriosis. Sex Reprod Healthc. 2012;3(2):93–94.

31.

Wickstrom

Bruse

Sjosten

Spira

Edelstam

. Pertubation with lignocaine as a new treatment of dysmenorrhea due to endometriosis: a randomized controlled trial. Hum Reprod. 2012;27(3):695–701.

32.

Wickstrom

Bruse

Sjosten

Spira

Edelstam

. Quality of life in patients with endometriosis and the effect of pertubation with lidocaine - a randomized controlled trial. Acta Obstet Gynecol Scand. 2013;92(12):1375–1382.

33.

Edelstam

Sjosten

Bjuresten

Wanggren

Spira

. A new rapid and effective method for treatment of unexplained infertility. Hum Reprod. 2008;23(4):852–856.

34.

Kubista

Andrade

Bengtsson

. The real-time polymerase chain reaction. Mol Aspects Med. 2006;27(2-3):95–125.

35.

Girard

Atlan

Bencharif

. New insights into lidocaine and adrenaline effects on human adipose stem cells. Aesthetic Plastic Surg. 2013;37(1):144–152.

36.

Tsai

Hsu

Chueh

Wong

. Lidocaine attenuates monocyte chemoattractant protein-1 production and chemotaxis in human monocytes: possible mechanisms for its effect on inflammation. Anesth Analg. 2003;97(5):1312–1316.

37.

Bedaiwy

Falcone

. Peritoneal fluid environment in endometriosis. Clinicopathological implications. Minerva Ginecol. 2003;55(4):333–345.

38.

Bredhult

Sahlin

Olovsson

. Gene expression analysis of human endometrial endothelial cells exposed to op′-DDT. Mol Hum Reprod. 2008;14(2):97–106.

39.

Bredhult

Backlin

Olovsson

. Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation. Hum Exp Toxicol. 2007;26(10):801–809.

40.

Helmestam

Stavreus-Evers

Olovsson

. Cadmium chloride alters mRNA levels of angiogenesis related genes in primary human endometrial endothelial cells grown in vitro. Reprod Toxicol. 2010;30(3):370–376.