Prospective Changes in Serum Levels of Some Proinflammatory Cytokines and Erythropoietin among Anaemic HIV-infected Patients Attending Kenyatta National Hospital Comprehensive Care Centre

Authors

  • Jackson Ireri Kenyatta University, P.O Box 43844-00100, Nairobi, Kenya
  • Joseph Ngeranwa Kenyatta University, P.O Box 43844-00100, Nairobi, Kenya
  • David Mburu Kenyatta University, P.O Box 43844-00100, Nairobi, Kenya
  • Walter Jaoko University of Nairobi, P.O Box 30197-00100, Nairobi Kenya
  • Christine Sekadde-Kigondu University of Nairobi, P.O Box 30197-00100, Nairobi Kenya
  • Peter Wanzala Kenya Medical Research Institute, P.O Box 20778-00202, Nairobi Kenya

Keywords:

Proinflamatory cytokines, erythropoietin, anaemia, Human immunodeficiency Virus.

Abstract

Between 70 to 80% of HIV infected patients develop anaemia which is a major complication in advanced HIV infection. The multifactorial etiology of the HIV-associated anaemia requires extensive studies on its unique pathophysiology as a step towards improving therapeutic options and disease management.The objective of this study is to monitor changes in serum levels of erythropoietin (Epo), Tumor necrosis factor-alpha (TNF-?), Interleukin-6 (IL-6), C-Reactive Protein (CRP) and anaemia in HIV infected patients over six months’ period. This study is Longitudinal descriptive study and it was conducted at Kenyatta National Hospital, Kenyatta National Hospital can be considered as Comprehensive Care Centre.

The study used one hundred and eighty-four (184) seropositive adults aged 18 to 60 years.The results shows that Blood cells exhibited pathologies ranging from: Rouleaux formation, round macrocytes, microcytic hypochromic cells and target cells in frequencies that decreased with increase in CD4+ cells. Normochromic, macrocytic normochromic and dimorphic anaemias were observed. Bicytopenia (erythrocytopenia and leucopenia), reactive thrombocytosis with giant platelets, neutrophil and eosinophil hypersegmentations were also observed. Persistent increase in Epo and CRP levels were demonstrated among subjects throughout the study period. Increases in TNF-? levels without corresponding increase in IL-6 levels were observed. Persistence anaemia in presence of high Epo levels is suggestive of hyposensitivity to Epo by erythroid precursors. Asynchronized increases in TNF-? and IL- 6 levels may have deprived the duo the synergy required to effectively inhibit Epo production further facilitating the escalating levels of Epo observed. High levels of CRP observed indicate enhanced inflammation processes associated with HIV infection. Iron studies to rule out the role of iron-restricted erythropoiesis in the development microcytic, dimorphic anaemias and the granulocytic hypersegmentations noted are recommended. Studies on the possibility of Epo hyposensitivity derailing the effectiveness of recombinant human Epo in the management of HIV – associated anaemia are recommended.        

References

. M. Meidani, F. Rezaei, R.M. Maracy, et al. “Prevalence, severity, and related factors of anemia in HIV/AIDS patients”. Journal of Research in Medical Sciences. Vol. 17 (2): 138–42, 2012.

. G. Ferede and Y. Wondimeneh. “Prevalence and related factors of anemia in HAART-naïve HIV positive patients at Gondar University Hospital, Northwest Ethiopia”. BIOMed Central Haematology. Vol 13:8. doi: 10.1186/2052-1839-13-8. 2013.

. A.A. Adewumi, A.A. Titilope. and V.A. Osamuedemen. “Prevalence of HIV- related autoimmune haemolytic anaemia in Lagos, Nigeria”. Nigerian Medical Journal. Vol. 55 (1): 63–6, 2014.

. J.J. Carrero, A.R. Qureshi, A. Nakashima, et al. “Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease”. Nephrology Dialysis Transplantation. Vol. 27 (2):709-15, 2012.

. V. Ruchira, C. Diazzi, D. Santi, et al. “Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study”. Andrology. Vol. 3:298, 2015.

. A. Redig. and N. Berliner. “Pathogenesis and clinical implications of HIV-related anemia”. American Society of Hematology, the education programme. 377-81, 2013.

. A. Amanzada, A.D. Goralczyk, L. Reinhardt, et al. “Erythropoietin rs1617640 G allele associates with an attenuated rise of serum erythropoietin and a marked decline of hemoglobin in hepatitis C patients undergoing antiviral therapy”. BioMed Center Infectious Diseases 14: 503.DOI: 10.1186/1471-2334-14-503, 2011

. G.N. Beverborg, N. Verweij, T. Klip et al. “Erythropoietin in the General Population: Reference Ranges and Clinical, Biochemical and Genetic Correlates” PLoS ONE 10 (4): e0125215. doi: 10.1371/journal.pone.0125215, 2015.

. D.T. Jamison, R.G. Feachem, M.W. Makgoba, et al. “Disease and mortality in Sub-Saharan Africa. 2nd edition, Washington” (DC). World Bank Chapter 1, 2006.

. C. Popa, M.B. Netea, P.L. Van Riel, et al. “The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk”. The Journal of Lipid Research.Vol.48: 751- 62, 2007.

. A.V. Hoffbrand, D. Catovsky and E.G. Tuddenham. Postgraduate haematology; 4th edition. Blackwell publication. 2005, Pp.352- 3.

. D.K. Gatukui, G.O. Oyoo, J. Rajab, et al. “Serum erythropoietin in patients with anaemia on HAART attending the Kenyatta National Hospital, Comprehensive Care Centre”. East African Medical Journal of pathology. Vol.1: 2-6, 2014.

. B. Enawgaw, M. Alem, M. Melku, et al. “Prevalence and associated risk factors of anemia among HIV infected children attending Gondar university hospital, Northwest Ethiopia: a cross sectional study”. BioMed Central Hematology. Vol. 15:12, 2015.

. J. Ford. "Red blood cell morphology". International Journal of Laboratory Hematology. Vol.35 (3): 351-7, 2013.

. J. Kaferle and C.E. Strzoda. “Evaluation of macrocytosis.” American Family Physician.Vol. 79 (3):203 – 8, 2009.

. D.D. Richman, M.A. Fischl, M.H. Grieco, et al. “The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo- controlled trial.” New England Journal of Medicine. Vol. 317:192-7, 1987.

. . Oliveira, R.A. Oliveira and L.R. Souza. “Impact of antiretroviral therapy on occurrences of macrocytosis in patients with HIV/AIDS in Maringá, State of Paraná.” Revista da Sociedade Brasileira de Medicina Tropical. Vol.44 (1):26-29, 2011.

. T.L. Fabry. “Mechanism of erythrocyte aggregation and sedimentation”. Blood. Vol.70 (5):1572 – 6, 1987.

. C.R. Huang. “Thixotropic properties of whole blood from healthy human subjects”. Biorheology.Vol. 24 (6):795-801, 1987.

. . Kaewketthong, A. Bunyaratvej and S. Barusrux. “Different cell volume with high target cell population between liver disease and homozygous hemoglobin”. E. Journal of the Medical Association of Thailand. Vol. 75(1):228-32, 1992.

. S. Langford, J. Ananworanich and D. Cooper. “Predictors of Disease Progression in HIV Infection”. A review. AIDS Research and Therapy. Vol.4:11, 2007.

. G. Ferede and Y. Wondimeneh.” Prevalence and related factors of anemia in HAART-naïve HIV positive patients at Gondar University Hospital, Northwest Ethiopia”. BIOMed Central Haematology.Vol. 13:8. doi: 10.1186/2052-1839-13-8, 2013

. L. Hallberg. “Iron balance in pregnancy. In: Berger H. Vitamins and minerals in pregnancy and lactation”. New York, Raven Press.; 115-27, 1988

. l.R. Ear and C.E. Woteki. “Iron deficiency anemia: recommended guidelines for the prevention, detection, and management among U.S. children and women of childbearing age”. Washington, DC: National Academy Press, 1993.

. T. Ansari , L. Ali , T. Aziz, et al. “Nutritional iron deficiency in women of child bearing ages-what to do?” Journal of Ayub Medical College, Abbottabad Vol. 21(3):17-20, 2009.

. S.S. Parinitha and H.M. Kulkarni. “Haematological changes in HIV infection with correlation to CD4 cell count.” Australia Medical Journal. Vol. 5 (3):157-62, 2012.

. S.E. Mathews, D. Srivastava, R.B. Yadav and A. Sharma. “Association of haematological profile of human immunodeficiency virus-positive patients with clinicoimmunologic stages of the disease”. Journal of laboratory physicians. Vol. 5 (1): 34 -7, 2013.

. M. Edberg and B. Hayes. “Profile of HIV-Infected Hispanics with Pancytopenia”. International Journal of Environmental Research and Public Health. Vol. 13 (1):3, 2015

. P. Vishnu and D.M. Aboulafia. “Haematological manifestations of human immune deficiency virus infection”. British Journal of Haematology. Vol. 171 (5): 695–709, 2015.

. G.C. Santis, D.M. Brunetta, F.C. Vilar, et al. “Hematological abnormalities in HIV-infected patients”. International Journal of Infectious Diseases. Vol. 15 (12): e808-e811, 2011.

. M.M. Rahman, S. Giti, M.S. Islam and M.M. Rahman. “Haematological Changes in Peripheral Blood of HIV –Infected Persons with Correlation to CD4 Cell Count”. Journal of Bangladesh College of Physicians and Surgeons. Vol. 32:130-6, 2014.

. C.S. Devi, S. Satish and M. Gupta. “Study of Haematological Profile in Human Immune Deficiency Virus Infection: Correlation with CD4 Counts”. Annals of Pathology and Laboratory Medicine. Vol. 3 (5): Nov. 2016 Supplement.

. S. Micali. “Mechanism for the T4 lymphopenia of AID”. Immunology. Vol. 90: 10982-3, 1993.

. V.D. Ryst, K. Marindé, J. Gina, S. Marita, et al. “Correlation among Total Lymphocyte Count, Absolute CD4+ Count, and CD4+ Percentage in a Group of HIV-1-Infected South African Patients”. Cornea Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology. Vol. 19 (3):238 – 44, 1998.

. A. Gelaw, Y. Shiferaw and R. Molla. “Absolute lymphocyte counts as a surrogate marker for CD4+ cell count in monitoring of antiretroviral therapy, Northwest Ethiopia: retrospective evaluation.” Asian Pacific Journal of Tropical Disease. Vol. 3 (4):262 - 6, 2013.

. D.A. Westerman, D. Evans and J. Metz. “Neutrophil hypersegmentation in iron deficiency anaemia: a case-control study”. British Journal Haematolology. Vol. 107 (3):512- 5, 1999.

. T. Sipahi, B. Tavil and Y. Unver. “Neutrophil hypersegmentation in children with iron deficiency anemia”. Journal of Pediatric Haematology and Oncology.Vol. 19 (4):235-8, 2002.

. S. Duggen, Y. Yıldırmak and F. Cetinkaya. “Neutrophil hypersegmentation and thrombocytosis in children with iron deficiency anaemia.” The Turkish Journal of Pediatrics. Vol. 47: 251 - 4, 2005.

. A. Özcan, A. Toraman, et al. “Evaluation of leucocyte and its subgroups in iron deficiency anemia”. International Journal of Medicine and Medical Sciences. Vol.3 (5): 135 – 8, 2011.

. A.S. Adewoyin and B. Nwogoh. “Peripheral Blood Film - A review”. Annals of Ibadan Postgraduate Medicine. Vol. 12 (2): 71–9, 2014.

. T. Hussain, S.W. Abbas and F.S. Zareen. “Reactive Thrombocytosis following acute infection and pancytopenia”. Pakistan Armed Forces Medical Journal. Vol. 58 (2):219-22, 2008.

. G.B. Madaan, Z.S. Jairajpuri, F.F. Hajini and S. Jetley. “Postoperative thrombocytosis: An unusual case report”. International Journal of Applied Basic Medical Research. Vol.5 (3):225 - 7, 2015.

. I. Kazama, Y. Endo, H. Toyama, et al. “Compensatory Thrombopoietin Production from the Liver and Bone Marrow Stimulates Thrombopoiesis of Living Rat Megakaryocytes in Chronic Renal Failure”. Nephron Extra. Vol. 1:147-56, 2011.

. B.N. Grote, N. Verweij, I.T. Klip, et al. “Erythropoietin in the general population: Reference ranges and clinical, biochemical and genetic correlates.” PLoS ONE 10 (4), 2015.

. B.J. Bain. “Ethnic and sex differences in total and differential white cell count and platelet count”. Journal of Clinical Pathology. Vol. 49:664 – 6, 1996.

. E. Karita, N. Ketter, M.A. Price, et al. “CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa”. PLoS ONE 4 (2): e4401, 2009.

. A. Tsiakalos, J.G. Routsias, T. Lordosis, et al. “Fine epitope specificity of anti-erythropoietin antibodies reveal molecular mimicry with HIV-1 p17 protein: a pathogenetic mechanism for HIV-1-related anemia”. Journal of Infectious Diseases. Vol. 204 (6):902 – 11, 2011.

. P.S. Belperio and D.C. Rhew. “Prevalence and outcomes of anaemia in individuals with human immunodeficiency virus: a systematic review of the literature”. American Journal of Medicine. Vol. 116 (Supplement. 7A):27S - 43S, 2004.

. P. Aukrust, F. Muller, E. Lien, et al. “Tumor Necrosis Factor (TNF) System Levels in Human Immunodeficiency virus–Infected Patients during Highly Active Antiretroviral Therapy: Persistent TNF Activation Is Associated with Virologic and Immunologic Treatment Failure”. The Journal of Infectious Diseases. Vol. 179:74-82, 1999.

. K.V. Khanna, X.F. Xiao-Fang, D.H. Ford, et al. “Differences Among HIV-1 Variants in Their Ability to Elicit Secretion of TNF-a”. The Journal of Immunology. Vol. 164:1408 – 15, 2017.

. C.W. Faquin, T.J. Schneider and M.A. Goldberg. “Effect of Inflammatory Cytokines on Hypoxia-Induced Erythropoietin Production”. Blood. Vol. 79 (8): 1987- 94, 1992.

. J.G. Fieldman, P. Goodwasser, S. Holman, et al. “Reactive protein is an independent predictor of mortality in women in HIV-1 infection”. Journal of acquired immune deficiency syndrome. Vol. 32:210 – 14, 2003.

. M.M. Guimarães , D.B. Greco and S.M. Figueiredo. “High-sensitivity C- reactive protein levels in HIV-infected patients treated or not with antiretroviral drugs and their correlation with factors related to cardiovascular risk and HIV infection”. Atherosclerosis. Vol. 201(2):434-9, 2008.

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Published

2017-12-20

How to Cite

Ireri, J., Ngeranwa, J., Mburu, D., Jaoko, W., Sekadde-Kigondu, C., & Wanzala, P. (2017). Prospective Changes in Serum Levels of Some Proinflammatory Cytokines and Erythropoietin among Anaemic HIV-infected Patients Attending Kenyatta National Hospital Comprehensive Care Centre. International Journal of Sciences: Basic and Applied Research (IJSBAR), 36(8), 90–107. Retrieved from https://www.gssrr.org/index.php/JournalOfBasicAndApplied/article/view/8408

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