Differential expression of tumor necrosis factor alpha and interleukin 1 beta compared with interleukin 6 in monocytes from human immunodeficiency virus-positive individuals measured by polymerase chain reaction

Abstract

Expression of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) was evaluated in unstimulated peripheral blood monocytes obtained from human immunodeficiency virus-positive (HIV+) individuals using a reverse transcription-polymerase chain reaction (RT-PCR) method. In all, 40 subjects were included--13 asymptomatic, 11 with ARC, seven with AIDS, and nine HIV- controls. Of the asymptomatic individuals, 85% were positive for TNF alpha and IL-1 beta compared with only 27% of the ARC and 42% of the AIDS patients. Expression of IL-6 message was observed in lesser proportions, with no significant differences among disease states. Quantitation of IL-1 beta and TNF alpha mRNA from the positive samples fell into two categories, low responders (six of 17), with < 5,000 copies of IL-1 beta and TNF alpha mRNA, and high responders (11 of 17), with > 5,000 copies per 10 pg of total cellular RNA. There was no correlation of mRNA detection or concentration with CD4+ cell number or beta 2-microglobulin levels. However, the levels of mRNA, but not its presence alone, were positively correlated with neopterin levels. The data show differential cytokine regulation in monocytes, observed as an increase in the expression of TNF alpha and IL-1 beta compared with IL-6 in HIV+ patients. Our report also emphasizes the utility of an RT-PCR system in analyzing multiple cytokine transcript levels in small amounts of clinical materials.