Expression of adrenergic, acetylcholine and kappa opioid receptors on peripheral blood lymphocytes in patients with herpetic keratitis and those with idiopathic anterior and/or intermediate uveitis
DOI:
https://doi.org/10.31288/oftalmolzh2025438Keywords:
uveitis, herpetic keratitis, opioid receptors, β2 adrenergic receptors, corneaAbstract
Purpose: To assess the expression of adrenergic, acetylcholine (ACh) and opioid receptors on peripheral blood lymphocytes in patients with herpetic keratitis (HK) and those with idiopathic anterior and/or intermediate uveitis (IAIU).
Methods: Thirty one patients with HK (group 1; age, 40.7 ± 14.2 years), 36 patients with IAIU (group 2; age, 49.9 ± 12.5 years), and 12 healthy volunteers (controls; age, 43.5 ± 14.8 years) were included in the study and examined at Immunology laboratory, SI “The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine”. Immunocytochemistry with monoclonal antibodies to receptors and fluorescein microscopy were used. IBM SPSS Statistics software and spreadsheets were used for the statistical analysis.
Results: Expression of β adrenergic receptors, Ach receptors and kappa opioid receptors (KOR) on lymphocytes was significantly increased in patients with HK and patients with IAIU compared to healthy controls. There was a significant difference in the ratio of expression of β adrenergic receptors to KOR on peripheral blood lymphocytes (expressed as percentage) between patients with HK and healthy controls and between patients with IAIU and healthy controls.
References
Chhatar S, Lal G. Role of adrenergic receptor signalling in neuroimmune communication. Curr Res Immunol. 2021 Nov 25:2:202-217. https://doi.org/10.1016/j.crimmu.2021.11.001
Elkhatib SK, Case AJ. Autonomic regulation of T-lymphocytes: Implications in cardiovascular disease. Pharmacol Res. 2019 Aug 146:104293. https://doi.org/10.1016/j.phrs.2019.104293
Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004 Jul;130(4):601-30. https://doi.org/10.1037/0033-2909.130.4.601
Araujo LP, Maricato JT, Guereschi MG, Takenaka MC, Nascimento VM, Melo FM, et al. The sympathetic nervous system mitigates CNS autoimmunity via beta2-adrenergic receptor signaling in immune cells. Cell Rep. 2019 Sep 17;28(12):3120-3130.e5. https://doi.org/10.1016/j.celrep.2019.08.042
Kawashima K, Fujii T The lymphocytic cholinergic system and its contribution to the regulation of immune activity. Life Sci. 2003 Dec 26. 74(6): 675-696. https://doi.org/10.1016/j.lfs.2003.09.037
Cox MA, Duncan GS, Lin GHY, Steinberg BE, Yu LX, Brenner D et al. Choline acetyltransferase-expressing T cells are required to control chronic viral infection. Science. 2019 Feb 8;363(6427): 639-644. https://doi.org/10.1126/science.aau9072
Mueller S.N. Neural control of immune cell trafcking. J Exp Med. 2022 Mar 7: 219(3). https://doi.org/10.1084/jem.20211604
Harle P. Increase of sympathetic outfow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems. Ann Rheum Dis. 2006 Jan;65(1):51-6. https://doi.org/10.1136/ard.2005.038059
Quatrini L, Vivier S, Ugolini S. Neuroendocrine regulation of innate lymphoid cells. Immunol Rev. 2018 Nov;286(1):120-136. https://doi.org/10.1111/imr.12707
Yahyavi-Firouz-Abadi N, Tahsili-Fahadan P, Ostad SN. Effect of mu and kappa opioids on injury-induced microglial accumulation in leech CNS: involvement of the nitric oxide pathway. Neuroscience. 2007 Feb 9;144(3):1075-86. https://doi.org/10.1016/j.neuroscience.2006.10.036
Cheng B, Liu HW, Fu XB, Sheng ZY, Li JF. Co-existence and upregulation of three types of opioid receptors, mu, delta and kappa, in human hypertrophic scars. Br J Dermatol. 2008 Apr;158(4):713-20. https://doi.org/10.1111/j.1365-2133.2008.08449.x
Phan NQ, Bernhard J.D, Luger TA, Ständer S. An antitumor treatment with systemic µ-opioid receptor antagonists: a review. J Am Acad Dermatol. 2010 Oct;63(4):680-688. https://doi.org/10.1016/j.jaad.2009.08.052
Manglik A, Lin H, Shoichet BK. Structure-based discovery of opioid analgesics with reduced side effects. Nature. 2016 Sep 8;537(7619):185-190. https://doi.org/10.1038/nature19112
Arreola R, Alvarez-Herrera S, Pérez-Sánchez G, Becerril-Villanueva E, Cruz-Fuentes C, Flores E et al. Immunomodulatory effects mediated by dopamine. J Immunol Res. 2016:3160486. https://doi.org/10.1155/2016/3160486
Finlay MJ, Chen X, Bardi G, Davey P, Geller E.B, Zhang L et al. Bi-directional heterologous desensi tization between the major HIV-1 co-receptor CXCR4 and the kappa-opioid receptor. J Neuroimmunol. 2008; 197: 114-123. https://doi.org/10.1016/j.jneuroim.2008.04.021
Khramenko N, Usov V, Velychko L, Konovalova N, Bogdanova O Level of adrenoreception and acetylcholine reception on lymphocytes in peripheral blood in patients with anterior uveitis complicated by macular edema DOG 2021. Abstract A-1213-0052-00519
Gluzman DF, Skliarenko VA, Nagorna IA, Kryachok IA. Diagnostic immunocytochemistry of tumors. Kyiv:Morion, 2003. Russian.
Velychko LM, Bogdanova OV Method for studying the receptor-modifying effect of pharmacological immunotropic drugs on cell activation markers. Ukrainian patent UA 103483; 2015.
Khramenko NI, Velychko LN, Bogdanova OV, Konovalova NV, Zhuravok YuO. Sensitivity of peripheral blood lymphocytes to epinephrine and acetylcholine in patients with primary and recurrent posterior uveitis. Ophthalmol J. 2022 (4)3-11. Ukrainian. https://doi.org/10.31288/oftalmolzh20224311
Khramenko NI, Velichko LM, Bogdanova OV, Drozhzhina GI. Levels of adrenaline and acetylholine reception expression on T-lymphocytes in peripheric blood in pathients with recidiving stromal herpetic ceratites. AZƏRBAYCAN OFTALMOLOGİYA JURNALI ORİJİNAL MƏ4ALƏLƏR. 2022; 42(3);86-100. Russian.
Khramenko NI, Gaidamaka TB, Drozhzhyna GI, Velychko LN, Bogdanova AV. ICAM-1 expression on blood lymphocytes in patients with stromal herpes keratitis at diferent periods of disease. J Ophthalmol. 2020: 3: 23-28. Ukrainian. https://doi.org/10.31288/oftalmolzh202032328
Pavlov VA, Tracey KJ The vagus nerve and the inflammatory refex-linking immunity and metabolism. Nat Rev Endocrinol. 2012 Dec;8(12):743-54 https://doi.org/10.1038/nrendo.2012.189
Mousa SA, Shaqura M, Brendl U, Al-Khrasani M, Fürst S, Schäfer M. Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain. Brain Behav Immun. 2010 Nov;24(8):1310-23. https://doi.org/10.1016/j.bbi.2010.06.008
Stefano GB, Scharrer B, Smith EM, Hughes TK Jr, Magazine HI, Bilfinger TV, et al. Opioid and Opiate Immunoregulatory Processes. Crit Rev Immunol. 1996;16(2):109-44. https://doi.org/10.1615/CritRevImmunol.v16.i2.10
Labuz D, Celik MÖ, Seitz V, Machelska H. Interleukin-4 Induces the release of opioid peptides from M1 macrophages in pathological pain. J Neurosci. 2021 Mar 31; 41(13):2870-2882. https://doi.org/10.1523/JNEUROSCI.3040-20.2021
Sharp BM. Multiple opioid receptors on immune cells modulate intracellular signaling. Brain Behav Immun. 2006; 20(1):9-14 https://doi.org/10.1016/j.bbi.2005.02.002
Sanders VM. The beta2-adrenergic receptor on T and B lymphocytes: Do we understand it yet? Brain Behav Immun. 2012;26(2);195-200. https://doi.org/10.1016/j.bbi.2011.08.001
Husain S. Opioid receptors: methods for detection and their modes of actions in the eye. Methods Mol Biol. 2015: 1230; 243-251 https://doi.org/10.1007/978-1-4939-1708-2_20
Husain S, Potter DE, Crosson CE. Opioid receptor-activation: retina is protected from ischemic injury. Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3853-9. https://doi.org/10.1167/iovs.08-2907
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Velychko L. M., Bogdanova O. V., Khramenko N. I., Konovalova N. V., Drozhzhyna G. I., Sereda K. V.

This work is licensed under a Creative Commons Attribution 4.0 International License.
This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) that allows users to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author as long as they cite the source.
COPYRIGHT NOTICE
Authors who publish in this journal agree to the following terms:
- Authors hold copyright immediately after publication of their works and retain publishing rights without any restrictions.
- The copyright commencement date complies the publication date of the issue, where the article is included in.
DEPOSIT POLICY
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) during the editorial process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work with an acknowledgement of its initial publication in this journal.
- Post-print (post-refereeing manuscript version) and publisher's PDF-version self-archiving is allowed.
- Archiving the pre-print (pre-refereeing manuscript version) not allowed.