Supplementation With L-ornithine But Not L-arginine Increases Density of CD68+ and CD163+ Macrophages in Periodontitis
Summary
The aim of the study was to investigate whether oral administration of L-arginine or L-ornithine could modulate local representation density and ratio of macrophages in periodontitis-affected gingiva by using immunohistochemical detection of CD68+ and CD163+ macrophages in biopsies of the gingiva. The null hypothesis tested was that L-arginine and L-ornithine have no influences on CD68+ and CD163+ macrophages densities when supplementing the treatment of periodontitis. Materials and methods. 75 individuals with a diagnosis of generalized periodontitis at stages II-III and grade B (38 women and 37 men, 51% and 49%, respectively) were included in the study. Periodontitis was diagnosed by using the criteria of the Classification of Periodontal and Peri-Implant Diseases and Conditions 2017. 25 patients received scaling and root planing only; 25 patients additionally received L-arginine, and 25 - L-ornithine, according to instructions available in Ukraine. For the immunohistochemical study of paraffin-embedded sections, the gingival biopsy was taken from 5 selected patients per group before treatment and after 1 month. CD68+ (cluster of differentiation 68 positive) and CD163+ cells served as a morphological equivalent of M1, M2 macrophages subpopulations, and their densities were calculated per 10000 μm2. Statistical analysis was performed by adequate power methods.
Timeline
- Start
- 2017-10-20
- Primary completion
- 2018-10-02
- Completion
- 2018-11-01
Publications
- Background Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170. doi: 10.1111/jcpe.12946.
- Background Shinkevich VI, Kaidashev IP. [The role of immune cells factors in the remodeling of gingiva at chronic generalized periodontal disease]. Stomatologiia (Mosk). 2012;91(1):23-7. Russian.
- Background Zhou LN, Bi CS, Gao LN, An Y, Chen F, Chen FM. Macrophage polarization in human gingival tissue in response to periodontal disease. Oral Dis. 2019 Jan;25(1):265-273. doi: 10.1111/odi.12983. Epub 2018 Oct 12.
- Background Shynkevych VI, Kaidashev IP. Contribution of macrophage subpopulations to the pathogenesis of chronic periodontitis in humans and perspectives for study. Review of the literature. Zaporozhye medical journal. 2019;21(1): 137-143. doi:10.14739/2310-1210.2019.1.155863.
- Background Garaicoa-Pazmino C, Fretwurst T, Squarize CH, Berglundh T, Giannobile WV, Larsson L, Castilho RM. Characterization of macrophage polarization in periodontal disease. J Clin Periodontol. 2019 Aug;46(8):830-839. doi: 10.1111/jcpe.13156. Epub 2019 Jun 25.
- Background Allam JP, Duan Y, Heinemann F, Winter J, Gotz W, Deschner J, Wenghoefer M, Bieber T, Jepsen S, Novak N. IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions. J Clin Periodontol. 2011 Oct;38(10):879-86. doi: 10.1111/j.1600-051X.2011.01752.x. Epub 2011 Aug 31.
- Background Slots J. Periodontitis: facts, fallacies and the future. Periodontol 2000. 2017 Oct;75(1):7-23. doi: 10.1111/prd.12221.
- Background Almubarak A, Tanagala KKK, Papapanou PN, Lalla E, Momen-Heravi F. Disruption of Monocyte and Macrophage Homeostasis in Periodontitis. Front Immunol. 2020 Feb 26;11:330. doi: 10.3389/fimmu.2020.00330. eCollection 2020.
- Background Gordon S, Pluddemann A, Martinez Estrada F. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014 Nov;262(1):36-55. doi: 10.1111/imr.12223.
- Background Satoh T. [Functional diversity of disorder-specific macrophages]. Rinsho Ketsueki. 2018;59(6):805-811. doi: 10.11406/rinketsu.59.805. Japanese.
- Background Kedia-Mehta N, Finlay DK. Competition for nutrients and its role in controlling immune responses. Nat Commun. 2019 May 9;10(1):2123. doi: 10.1038/s41467-019-10015-4.
- Background Angajala A, Lim S, Phillips JB, Kim JH, Yates C, You Z, Tan M. Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism. Front Immunol. 2018 Jul 12;9:1605. doi: 10.3389/fimmu.2018.01605. eCollection 2018.
- Background Rath M, Muller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol. 2014 Oct 27;5:532. doi: 10.3389/fimmu.2014.00532. eCollection 2014.
- Background Nouwen LV, Everts B. Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape. Cells. 2020 Jan 9;9(1):161. doi: 10.3390/cells9010161.
- Background Hardbower DM, Asim M, Luis PB, Singh K, Barry DP, Yang C, Steeves MA, Cleveland JL, Schneider C, Piazuelo MB, Gobert AP, Wilson KT. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E751-E760. doi: 10.1073/pnas.1614958114. Epub 2017 Jan 17.
- Background Moinard C, Caldefie F, Walrand S, Felgines C, Vasson MP, Cynober L. Involvement of glutamine, arginine, and polyamines in the action of ornithine alpha-ketoglutarate on macrophage functions in stressed rats. J Leukoc Biol. 2000 Jun;67(6):834-40. doi: 10.1002/jlb.67.6.834.
- Background Liao SY, Showalter MR, Linderholm AL, Franzi L, Kivler C, Li Y, Sa MR, Kons ZA, Fiehn O, Qi L, Zeki AA, Kenyon NJ. l-Arginine supplementation in severe asthma. JCI Insight. 2020 Jul 9;5(13):e137777. doi: 10.1172/jci.insight.137777.
- Background Simsek B, Cakatay U. Could ornithine supplementation be beneficial to prevent the formation of pro-atherogenic carbamylated low-density lipoprotein (c-LDL) particles? Med Hypotheses. 2019 May;126:20-22. doi: 10.1016/j.mehy.2019.03.004. Epub 2019 Mar 9.
- Background Campion D, Giovo I, Ponzo P, Saracco GM, Balzola F, Alessandria C. Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis. World J Hepatol. 2019 Jun 27;11(6):489-512. doi: 10.4254/wjh.v11.i6.489.
- Background Ito N, Seki S, Ueda F. Effects of Composite Supplement Containing Collagen Peptide and Ornithine on Skin Conditions and Plasma IGF-1 Levels-A Randomized, Double-Blind, Placebo-Controlled Trial. Mar Drugs. 2018 Dec 3;16(12):482. doi: 10.3390/md16120482.
- Background Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210(2-4):153-60. doi: 10.1016/j.imbio.2005.05.010.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | L-arginine aspartate | Unknown | 1 g | Oral |
| Subject | L-ornithine aspartate | Unknown | 3 g | Oral |