High Levels of mRNA Encoding IL-4 in Unstimulated Peripheral Blood Mononuclear Cells from Tuberculosis Patients Revealed by Quantitative Nested Reverse Transcriptase-Polymerase Chain Reaction; Correlations with Serum IgE Levels

Abstract

The dominant view has been that there is little or no activation of Type 2 cytokine production in human tuberculosis. A novel approach to quantitative nested reverse transcriptase-polymerase chain reaction has revealed that this conclusion was based on technical inadequacies of earlier studies, particularly the failure to discriminate between IL-4 and the IL-4 splice variant, IL4 d 2. A new approach reveals that the largest cytokine change in tuberculosis is a 1-2 log increase in copy number for mRNAs encoding IL-4 and IL-13, accompanied by a small decrease in expression of mRNA encoding interferon-g. The increased IL-4 level correlates with disease severity and with serum levels of IgE and soluble CD30, and may be attributable to the recently observed increase in conversion of cortisone into cortisol in tuberculous lesions. The implications of these findings for pathogenesis, vaccine design and immunotherapy are discussed, as effective reagents will need to downregulate this inappropriate Th2 component.