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

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 t his conclusion was based on technical inadequacies of earlier studies, part icularly the failure to discriminate between IL-4 and the IL-4 splice varia nt, IL482. A new approach reveals that the largest cytokine change in tuber culosis is a 1-2 log increase in copy number for mRNAs encoding IL-4 and IL -13, accompanied by a smalt decrease in espression of mRNA encoding interfe ron-gamma. The increased IL-4 level correlates with disease severity and wi th serum levels of IgE and soluble CD30, and may be attributable to the rec ently observed increase in conversion of cortisone into cortisol in tubercu lous lesions. The implications of these findings far pathogenesis, vaccine design and immunotherapy are discussed, as effective reagents will need to downregulate this inappropriate Th2 component.