Interleukin 3 as an Erythropoietic Marker in Human Immunodeficiency Virus and Hepatitis B Positive Patients in South East Nigeria

Main Article Content

Chinenye E. Okenwa
Ijeoma C. Uzoma
Anulika O. Onyemelukwe
Ogechukwu C. Dozie- Nwakile
Hilary Emuebie
Victor C. Edeh
S. A. Ufelle

Abstract

Aim: To evaluate the interleukin 3 levels in some Hepatitis B virus and Human immunodeficiency virus (HIV) positive subjects.

Study Design: Cross sectional study.

Place and Duration of Study: Haematology Department, University of Nigeria Teaching Hospital Enugu, Nigeria, between June and September, 2019.

Methodology: A total of 86 subjects were recruited for this study; 40 were positive for the human immunodeficiency virus, 30 were Hepatitis B positive and 16 healthy subjects that served as controls. The controls had tested negative to Hepatitis B Virus, Human immunodeficiency Virus and hepatitis C virus infections. Whole blood samples were collected from the Human immunodeficiency Virus positive and control samples. Haemoglobin concentration was analysed using the Orphěe Mythic 22 automated analyzer. Serum samples collected from all 86 subjects were used to assay Interleukin 3 using the Enzyme Linked Immunosorbent assay based Finetest human interleukin 3 kit.

Results: A highly significant decrease in interleukin 3 levels was observed in Hepatitis B Virus and Human immunodeficiency virus positive subjects when compared with the apparently healthy control subjects, (P = 0.000 < 0.05). Average hemoglobin levels were also lower in the Human immunodeficiency virus subjects compared with the controls.

Conclusion: A reduction of the interleukin 3 may be part of the synergistic factors responsible for the anaemia usually seen in the viral infections.

Keywords:
Interleukin 3, haemoglobin, hepatitis B, human immunodeficiency virus, erythropoiesis, cytokines, growth factors

Article Details

How to Cite
Okenwa, C. E., Uzoma, I. C., Onyemelukwe, A. O., Nwakile, O. C. D.-, Emuebie, H., Edeh, V. C., & Ufelle, S. A. (2020). Interleukin 3 as an Erythropoietic Marker in Human Immunodeficiency Virus and Hepatitis B Positive Patients in South East Nigeria. Annual Research & Review in Biology, 35(6), 1-8. https://doi.org/10.9734/arrb/2020/v35i630231
Section
Original Research Article

References

Ford N, Vitoria M, Penazzato M, Doherty M, Shubber Z, Meintjes G, et al. Causes of hospital admission among people living with HIV worldwide: A systematic review and meta-analysis. Lancet HIV; 2015.

Parinitha S, Kulkarni M. Haematological changes in HIV infection with correlation to CD4 cell count. Australas Med J. 2012; 5(3):157.

Katemba C, Muzoora C, Muwanguzi E, Mwambi B, Atuhairwe C, Taremwa IM. Hematological abnormalities in HIV-antiretroviral therapy naïve clients as seen at an immune suppression syndrome clinic at Mbarara regional referral hospital, southwestern Uganda. J Blood Med. 2018;9:105–10.

Vishnu P, Aboulafia DM. Haematological manifestations of human immune deficiency virus infection. Br J Haematol; 2015.

Tincati C, Monforte A, Marchetti G. Immunological Mechanisms of Interleukin-2 (IL-2) Treatment in HIV/AIDS Disease. Curr Mol Pharmacol [Internet]. 2010;2 (1):40–5.

[Cited 2020 Mar 9]

Available:http://www.ncbi.nlm.nih.gov/pubmed/20021444

Singh A, Hungund B, Kumar L, Pattanshetti M. Clinico-haematological profile of patients with bicytopenia. Pathology; 2018.

Trépo C, Chan HLY, Lok A. Hepatitis B virus infection. Vol. 384, The Lancet. Lancet Publishing Group. 2014;2053–63.

Burnett RJ, Francois G, Kew MC, Leroux-Roels G, Meheus A, Hoosen AA, et al. Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: A call for further investigation. Liver International; 2005.

Chisari FV. Ferrari C. Hepatitis B Virus Immunopathogenesis. Annu Rev Immunol; 1995.

Akase IE, Musa BOP, Obiako RO, Ahmad Elfulatiy A, Mohammed AA. Immune Dysfunction in HIV: A Possible Role for Pro- and Anti-Inflammatory Cytokines in HIV Staging. J Immunol Res; 2017.

Sulkowski MS. Viral hepatitis and HIV coinfection. Journal of Hepatology; 2008.

Pascutti MF, Erkelens MN, Nolte MA. Impact of viral infections on hematopoiesis: From beneficial to detrimental effects on bone marrow output. Frontiers in Immunology; 2016.

Moore RD. Human Immunodeficiency Virus Infection, Anemia and Survival. Clin Infect Dis; 1999.

Khorami SHH, Nejatollahi F, Davarpanah MA. Serum levels of interleukin-4, interleukin-10 and interferon-γ in patients with chronic hepatitis B infection. Hepat Mon. 2018;18(4).

Robb L. Cytokine receptors and hematopoietic differentiation. Oncogene 2007 2647 [Internet]. 2007;26(47):6715–23.

Available:http://www.nature.com/articles/1210756

Filshie R. Cytokines in Haemopoietic Progenitor Mobilisation for Peripheral Blood Stem Cell Transplantation. Curr Pharm Des; 2005.

Ihle JN. Interleukin-3 and hematopoiesis. Chemical Immunology; 1992.

Lantz CS, Boeslger J, Song CH, Mach N, Kobayashi T, Mulligan RC, et al. Role for interleukin-3 in mast cell and basophil development and in immunity to parasites. Nature; 1998.

Metcalf D. Hematopoietic Cytokines. Blood [Internet]. 2008;111(2):485–91.

Available:http://www.ncbi.nlm.nih.gov/pubmed/18182579

Ihle JN, Pepersack L, Rebar L. Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine. J Immunol [Internet]. 1981; 126(6).

Available:https://www.jimmunol.org/content/126/6/2184

McBride WH, Dougherty GD, Wallis AE, Economou JS, Chiang CS. Interleukin-3 in gene therapy of cancer. Folia Biol (Praha); 1994.

Hornfeld H, Cruikshank W. Prospects for IL-16 in the Treatment of AIDS. Expert Opin Biol Ther [Internet]. 2001;1(3):425–32.

Available:http://www.ncbi.nlm.nih.gov/pubmed/11727516

Shao X, Ma J, Jia S, Yang L, Wang W, Jin Z. Interleukin-35 suppresses antiviral immune response in chronic hepatitis B virus infection. Front Cell Infect Microbiol; 2017.

Ng T, Marx G, Littlewood T, Macdougall I. Recombinant erythropoietin in clinical practice. Postgraduate Medical Journal; 2003.

Martí-Carvajal AJ, Solà I, Peña-Martí GE, Comunián-Carrasco G. Treatment for anemia in people with AIDS. Cochrane Database Syst Rev; 2011.

Guidotti LG, Guilhot,’ And S, Chisarii FV. Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and-independent pathwayst [Internet]. Journal of Virology. 1994.

[Cited 2020 Mar 9]

Available:http://jvi.asm.org/Downloadedfrom1266GUIDOTrIETAL

Scadden DT, Levine JD, Bresnahan J, Gere J, Mcgrath J, Wang Z, et al. In Vivo Effects of Interleukin 3 in HIV Type 1-Infected Patients with Cytopenia. AIDS Res Hum Retroviruses; 1995.

Falk S, Seipelt G, Ganser A, Ottmann O, Hoelzer D, Stutte H, et al. Bone Marrow Findings After Treatment With Recombinant Human interleukin-3. Am J Clin Pathol [Internet]. 1991;95(3):355–62.

Available:http://www.ncbi.nlm.nih.gov/pubmed/1996545

Morris KR, Bean AGD, Bruce MP, Broadway MM, O’Neil TE, Andrew ME, et al. Administration of porcine interleukin-3 induces increased levels of blood eosinophils. J Interf Cytokine Res [Internet]. 2008;28(7):435–43.

[Cited 2020 Mar 9]

Available:http://www.ncbi.nlm.nih.gov/pubmed/18597621

Ganser A, Lindemann A, Seipelt G, Ottmann O, Eder M, Falk S, et al. Effects of Recombinant Human interleukin-3 in Aplastic Anemia. Blood [Internet]. 1990; 76(7):1287–92.

Available:http://www.ncbi.nlm.nih.gov/pubmed/2207306

Lemoli RM, Fogli M, Fortuna A, Amabile M, Zucchini P, Grande A, et al. Interleukin‐11 (IL‐11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells. Br J Haematol. 1995;91(2):319–26.

[Cited 2020 Mar 9]

Available:http://doi.wiley.com/10.1111/j.1365-2141.1995.tb05296.x

Zhang J, Zhang Y, Wang Q, Li C, Deng H, Si C, et al. Interleukin-35 in immune-related diseases: protection or destruction. Immunology. Blackwell Publishing Ltd. 2019;157:13–20.

Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy - Review of a new approach. Pharmacological Reviews; 2003.

Gauvreau GM, Ellis AK, Denburg JA. Haemopoietic processes in allergic disease: Eosinophil/basophil development. Clinical and Experimental Allergy; 2009.

Kumar A, Devi SG, Kar P, Agarwal S, Husain SA, Gupta RK, et al. Association of cytokines in hepatitis E with pregnancy outcome. Cytokine. 2014;65(1):95– 104.

Du WJ, Zhen JH, Zeng ZQ, Zheng ZM, Xu Y, Qin LY, et al. Expression of Interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection. Diagn Pathol; 2013;

Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes; 2002.

Lin S-J, Shu PY, Chang C, Ng AK, Hu C. IL-4 Suppresses the Expression and the Replication of Hepatitis B Virus in the Hepatocellular Carcinoma Cell Line Hep3B. J Immunol. 2003;171(9):4708–16.

Kakumu S, Fuji A, Yoshioka K, Tahara H, Ohtani Y, Hirofuji H, et al. Pilot study of recombinant human interleukin 2 for chronic type B hepatitis. Hepatology [Internet]. 1988;8(3):487–92.

[Cited 2020 Mar 9]

Available:http://doi.wiley.com/10.1002/hep.1840080309

Bouezzedine F, Fardel O, Gripon P. Interleukin 6 inhibits HBV entry through NTCP down regulation. Virology. 2015 Jul 1;481:34–42.

Watashi K, Liang G, Iwamoto M, Marusawa H, Uchida N, Daito T, et al. Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis b virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID). J Biol Chem. 2013;288(44):31715–27.

Hösel M, Quasdorff M, Wiegmann K, Webb D, Zedler U, Broxtermann M, et al. Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection. Hepatology [Internet]. 2009;50 (6):1773–82.

[Cited 2020 Mar 9]

Available:http://www.ncbi.nlm.nih.gov/pubmed/19937696

Li X, Liu X, Tian L, Chen Y. Cytokine-mediated immunopathogenesis of hepatitis B virus infections. Clinical Reviews in Allergy and Immunology. Humana Press Inc. 2016;50:41–54.

Onishi RM, Gaffen SL. Interleukin-17 and its target genes: Mechanisms of interleukin-17 function in disease. Immunology; 2010.

Zhou Y, Zhang H, Li Y. IL-35 expression in peripheral blood CD4+ T cells from chronic hepatitis B virus-infected patients directly correlates with virus load. Cytokine; 2015.

Takebe N, Paredes J, Pino M, Lownsbury W, Agosti J, Krown S. Phase I/II Trial of the type i soluble recombinant human interleukin-1 receptor in HIV-1-infected Patients. J Interferon Cytokine Res [Internet]. 1998;18(5): 321–6.

Available:http://www.ncbi.nlm.nih.gov/pubmed/9620359

Frank AC, Zhang X, Katsounas A, Bharucha JP, Kottilil S, Imamichi T. Interleukin-27, an anti-HIV-1 cytokine, inhibits replication of hepatitis C virus. J Interf Cytokine Res; 2010.

Xiang XG, Xie Q. IL-35: A potential therapeutic target for controlling hepatitis B virus infection. J Dig Dis; 2015.

Xia Y, Protzer U. Control of hepatitis B virus by cytokines. Viruses. MDPI AG. 2017;9.

Cheng ST, Yuan D, Liu Y, Huang Y, Chen X, Yu HB, et al. Interleukin-35 level is elevated in patients with chronic hepatitis B virus infection. Int J Med Sci. 2018; 15(2):188–94.

Teng DK, Liu Y, Lv YF, Wang L, Zhang W, Wang JP, et al. Elevated interleukin-35 suppresses liver inflammation by regulation of T helper 17 cells in acute hepatitis B virus infection. Int Immunopharmacol; 2019.

Yang L, Jia S, Shao X, Liu S, Zhang Q, Song J, et al. Interleukin-35 modulates the balance between viral specific T cells and T helper 17 cells in chronic hepatitis B virus infection. 2019;(218):1–10.

Shlomai A, Schwartz RE, Ramanan V, Bhatta A, De Jong YP, Bhatia SN, et al. Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. Proc Natl Acad Sci U S A; 2014.

Anastassakos C, Alexander GJM, Wolstencroft RA, Avery JA, Portmann BC, Panayi GS, et al. Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection. Gastroenterology. 1988; 94(4):999–1005.

Freeman ML, Shive CL, Nguyen TP, Younes SA, Panigrahi S, Lederman MM. Cytokines and T-Cell Homeostasis in HIV Infection. J Infect Dis [Internet]. 2016; 214:S51–7.

[Cited 2020 Mar 9]

Available:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373575/

Spivak JL, Barnes DC, Fuchs E, Quinn TC. Serum immunoreactive erythropoietin in HIV-infected patients. JAMA J Am Med Assoc; 1989.

O’Connell C, Levine AM. Managing anemia in HIV-positive women. Vol. 2, Women’s Health. 2006;159–65.

Makubi A, Okuma J, Spiegelman D, Hawkins C, Darling AM, Jackson E, et al. Burden and determinants of severe anemia among HIV-infected adults: Results from a large urban HIV Program in Tanzania, East Africa. J Int Assoc Provid AIDS Care. 2015;14(2): 148–55.

Parinitha SS, Kulkarni MH. Haematological changes in HIV infection with correlation to CD4 cell count. Australas Med J; 2012.

Mangi M, Newland A. Interleukin-3 in hematology and oncology: Current State of knowledge and future directions. cytokines cell mol ther [Internet]. 1999;5 (2):87–95.

Available:http://www.ncbi.nlm.nih.gov/pubmed/10515681