HIV‐exposed uninfected infants: elevated cord blood Interleukin 8 (IL‐8) is significantly associated with maternal HIV infection and systemic IL‐8 in a Kenyan cohort

Abstract

Background In low and middle income countries, human immunodeficiency virus (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and mortality than their unexposed counterparts. To determine possible immune correlates of this effect, we investigated the impact of in utero HIV exposure on the uninfected neonatal immune milieu and maternal factors mediating these abnormalities in a cohort of vaginally delivered mother-infants. Samples of delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while 19 Kenyan HIV-uninfected (HU) women and their infants were selected from a control cohort. Results Compared to HU cord plasma, HEU cord plasma contained significantly higher levels of pro-inflammatory cytokines interleukins (IL)-6 and -8 (both p < 0.001) and significantly lower levels of CXC motif chemokine 11 (CXC11) (p < 0.001). Mediation analysis demonstrated that maternal HIV infection status was a significant determinant of infant IL-8 responses: HEU status was associated with a ninefold higher infant:mother (cord:delivery) plasma levels of IL-8 (p < 0.005), whereas maternal viral load was negatively associated with HEU IL-8 levels (p = 0.04) and not associated with HEU IL-6 levels. Conclusions Exposure to maternal HIV infection drives an increase in prenatal IL-8 that is partially mediated by maternal cytokine levels. Differences between maternal and infant cytokine levels strongly suggest independent modulation in utero, consistent with prenatal immune activation. Elevated pro-inflammatory signals at birth may interfere with T cell responses at birth and subsequently influence immune maturation and the risk of morbidity and mortality in HEU infants.

Immunologic biomarkers, morbidity and mortality among HIV patients hospitalised in a Tertiary Care Hospital in the Brazilian Amazon

“…In this context, an elevated IL-8 level was considered to be a factor associated with higher mortality in HIV/AIDS patients with opportunist infections, especially those precipitating respiratory disorders such as bacterial, viral and fungal pneumonia [ 35 – 40 , 46 , 47 ]. Therefore, our findings are in agreement with studies that show that IL-8 may be used as a serological predictor for death in a scenario of advanced HIV/AIDS with TB and fungal coinfections [ 46 , 48 – 52 ].…”

The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

“…Elevated cord plasma cytokines, including CXCL8, have been previously observed in some neonates born to SARS-CoV-2-positive mothers 17 . Similarly, increased cord plasma CXCL8 has been observed after in utero exposure to infection 36,37 , suggesting that maternal infection can directly influence fetal CXCL8. Raised neonatal inflammatory markers do appear to be related to the maternal infection status at the time of birth, as such profiles are less obvious in neonates born to mothers with recovered infection.…”

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

“…HEU infants show aberrations of the immune system at birth [ 55 – 57 ] with systemic immune activation [ 56 , 58 ] which could be linked to adverse health outcomes [ 59 , 60 ]. HEU infants also have lower antibody titres following vaccination [ 61 , 62 ] with abnormal B- and T-lymphocyte phenotypic profiles [ 63 , 64 ].…”