Interleukin-6 synthesis and IgE overproduction in children with perinatal human immunodeficiency virus-type 1 infection.

Abstract

Unbalanced interleukin network and elevated IL-6 synthesis are suggested mechanisms of immunoglobulin overproduction in children with perinatal human immunodeficiency virus-type 1 (HIV-1) infection. To investigate whether elevated IL-6 synthesis is a general mechanism of immunoglobulin overproduction in perinatal HIV-1 infection. In vitro spontaneous and phytohaemoagglutinin (PHA)-stimulated IL-6 and IL-2 synthesis, serum IgE, IgG, IgA, and IgM levels, CD4+ T-lymphocyte counts, and HIV-1 RNA copy numbers were cross-sectionally determined in 31 children with perinatal HIV-1 infection. Children with immunoglobulin z-scores in the highest quartile were defined as children with high immunoglobulin level. Relationships between interleukin synthesis, high immunoglobulin levels, and HIV-1 related disease were studied. Children with high IgE levels had higher spontaneous IL-6 synthesis (1337 +/- 138 pg/mL) compared with those without high IgE levels (861 +/- 194 pg/mL; P < .001). By contrast, spontaneous IL-6 synthesis was similar in children with or without high IgG, IgA, or IgM levels. Decreased PHA-stimulated IL-2 synthesis, low CD4+ lymphocyte counts, elevated HIV-1 RNA copy numbers, and severe disease correlated with high IgE (but not IgG, IgA, and IgM) levels. IgG, IgA, and IgM levels correlated with each other, but not with IgE levels. The increased IL-6 synthesis in HIV-1+ children may affect IgE rather than other immunoglobulin isotype levels. Overall results suggest that IgE and IgG, IgA, IgM overproduction have distinct underlying mechanisms.