Abstract
Objective
To determine the cytokine profile of HIV infected women treated with highly active anti-retroviral therapy (HAART) of variable duration in pregnancy.
Methods
HIV infected women were enrolled at a large tertiary hospital in Durban, South Africa in their antenatal period and stratified into those that initiated HAART before pregnancy (pre-pregnancy HAART or PPH group) and those who initiated HAART during pregnancy (in-pregnancy HAART or IPH group). These were compared with HIV negative women (HN group), matched for gestational age at the time of enrolment. Serum was obtained and Th1 and Th2 cytokines expression determined using the Bio-Plex Pro™ Human Cytokine Treg Panels.
Results
The overall cytokine profile of the cohort was pro-inflammatory as a result of significant IL-6 and TNF alpha expression. The anti-inflammatory markers (i.e. Th2 cytokines, namely IL4 and IL10) were poorly expressed by the whole cohort, with IL 4 seen almost exclusively in the IPH group, thus counter-balancing the predominantly pro-inflammatory milieu only in this group. PPH group had a pro-inflammatory milieu comparable to the HN control. IL 6 was the predominant cytokine in all groups, and as expected, it increased with advancing gestation in all the groups. This highly pro-inflammatory milieu was unexpected and needs further review
Conclusion
Long use of HAART suppresses the anti-inflammatory markers previously reported to be conducive for the wellbeing of pregnancy. This effect needs further review as it was similarly observed in our HIV uninfected controls.
Similar content being viewed by others
References
Saito S, Nakashima A, Shima T, Ito M. Th1, Th2, Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010;63:601–10.
Dutta S, Sengupta P. Defining pregnancy phases with cytokine shift. J Preg Reprod. 2017;1(4):1–3.
Raghupathy R. Cytokines as key players in the pathophysiology of preeclampsia. Med Princ Pract. 2013;2013:8–19.
Sykes L, MacIntyre D, Yap X, Teoh T, Bennet PR. The Th1:Th2 dichotomy of pregnancy and preterm labour. Mediat Inflamm. 2012;2012:1–12. https://doi.org/10.1155/2012/967629.
Brogin MJ, Cirino Ruocco AM, Vernini JM, Rudge MV, Calderon IM. Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetrics. ISRN Obstet Gynecol. 2012;2012:230742.
Moreli JB, Ruocco AM, Vernini JM, Rudge MV, Calderon IM. Interleukin 10 and tumor necrosis factor-alpha in pregnancy: aspects of interest in clinical obstetrics. ISRN Obstet Gynecol. 2011;2012:1–5. https://doi.org/10.5402/2012/230742.
Thaxton JE, Sharma S. Interleukin-10: a multi-faceted agent of pregnancy. Am J Reprod Immunol. 2010;63:482–91. https://doi.org/10.1111/j.1600-0897.2010.00810.
Azizieh F, Raghupathy R. IL-10 & pregnancy complications. Clin Exp Obstet Gynecol. 2017;44:252–8. https://doi.org/10.12891/ceog3456.2017.
Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. 2000;15:713–8. https://doi.org/10.1093/humrep/15.3.713.
Février M, Dorgham K, Rebollo A. CD4+ T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis. Viruses. 2011;3:586–612. https://doi.org/10.3390/v3050586.
Wambani JR, Kiboi NG, Makori WM, Ogola PE, Rachuonyo HO. Immunological profiles in HIV positive patients with or without opportunistic infections and the influence of highly active antiretroviral therapy: a systematic review and update. J Clin Cell Immunol. 2016;7:429. https://doi.org/10.4172/2155-9899.1000429.
Maharaj NR, Phulukdaree A, Nagiah S, Ramkaran P, Tiloke C, Chuturgoon AA. Pro-inflammatory cytokine levels in HIV infected and uninfected pregnant women with and without preeclampsia. PLoS ONE. 2017;12(1):e0170063. https://doi.org/10.1371/journal.pone.0170063.
Ewenighi-Amankwah CO, Onyenekwe CC, Udemba O, et al. A mother-to-child transmission study in Nigeria: the impact of maternal HIV infection and HAART on plasma immunoglobulins, cytokine profiles and infant outcome. Virol Sin. 2020. https://doi.org/10.1007/s12250-020-00202-9.
Sebitloane HM, Moodley J, Sartorius B. Associations between HIV, highly active anti-retroviral therapy, and hypertensive disorders of pregnancy among maternal deaths in South Africa 2011–2013. Int J Gynecol Obstet. 2017;136:195–9.
Moodley D, Moodley P, Sebitloane M, et al. High prevalence and incidence of asymptomatic sexually transmitted infections during pregnancy and postdelivery in KwaZulu Natal, South Africa. Sex Transm Dis. 2015;42(1):43–7. https://doi.org/10.1097/OLQ.0000000000000219.
Joyisa N, Moodley D, Nkosi T, et al. Asymptomatic bacterial vaginosis in pregnancy and missed opportunities for treatment: a cross-sectional observational study. Infect Dis Obstet Gynecol. 2019;2019:7808179. https://doi.org/10.1155/2019/7808179.
Kumar SB, Rice CE, Milner DA Jr, Ramirez NC, Ackerman WE, Mwapasa V, Turner AN, Kwiek JJ. Elevated cytokine and chemokine levels in the placenta are associated with in utero HIV-1 mother-to-child transmission. AIDS. 2012;26:685–94. https://doi.org/10.1097/QAD.0b013e3283519b00.
Richardson K, Weinberg A. Dynamics of regulatory T-cells during pregnancy: effect of HIV infection and correlations with other immune parameters. PLoS ONE. 2011;6:e28172. https://doi.org/10.1371/journal.pone.0028172.
Acknowledgements
We acknowledge the work of the research assistants, Grace Dlamini and Zama Khubone in the collection of data, statistician Partson Tinarwo in data analysis and Dr Charlette Tiloke for the manuscript preparations.
Author information
Authors and Affiliations
Contributions
All authors have contributed to the concept, data collection (HMS), data interpretation (HMS), writing and approving the final manuscript (HMS, TN and JM).
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Additional information
Responsible Editor: John Di Battista.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sebitloane, H.M., Naicker, T. & Moodley, J. The impact of the duration of HAART on cytokine profiles in pregnancy. Inflamm. Res. 69, 1053–1058 (2020). https://doi.org/10.1007/s00011-020-01375-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-020-01375-5