Cytokine profiles in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy

Abstract

Context: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children.

Objective: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection.

Setting: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong.

Patients: Ten Asian and 2 Eurasian children infected with HIV-1 by mother-to-child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART).

Main outcome measures: Numbers of unstimulated and mitogen-activated cytokine-secreting cells (IFN-gamma, interleukin [IL]-2, IL-4, IL-6, IL-10, IL-12, and TNF-alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads.

Results: Mitogen-stimulated IL-2-secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A-induced IFN-gamma, Con A-induced IL-4, and unstimulated IL-10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN-gamma, IL-2-, IL-4-, and IL-12-secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3-4 years of treatment but declined thereafter.

Conclusions: Alterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme-linked immunospots (ELISPOTs) could contribute to pediatric patient management.

Figures

Figure 1

Multiple regression correlation of numbers of IL-2-secreting cells/106 PBMCs with CD4+ and CD8+ T-cell counts in 12 pediatric patients treated with HAART. (A) IL-2 PHA vs CD4%, P = .0149; (B) IL-2 Con A vs CD4%, P = .0109; (C) IL-2 PHA vs CD4/mcL, P = .0008; (D) IL-2 Con A vs CD8%, P = .0196; (E) IL-2 PHA vs CD8/mcL, P = .0008; (F) IL-2 Con A vs CD4:CD8, P = .0035

Figure 2

Multiple regression correlations of virus load with numbers of (A) Con A-induced IFN-gamma-secreting cells/106 PBMCs, P = .0231; (B) Con A-induced IL-4-secreting cells/106 PBMCs, P = .0294; (C) unstimulated IL-10-secreting cells/106 PBMCs, P = .0015. The data were log-transformed.

Figure 3

Numbers of IFN-gamma, IL-2, IL-4, and IL-12-secreting cells in 12 pediatric patients treated with HAART. Cytokine-secreting cells tended to increase for the first 3–4 years of treatment but declined thereafter. Curves were fitted by nonlinear regression.

Figure 4

Numbers of IL-6, IL-10, and TNF-alpha-secreting cells in 12 pediatric patients treated with HAART. Cytokine-secreting cells tended to remain stable over the study period. Curves were fitted by nonlinear regression.