The stability of mRNA encoding IL-4 is increased in pulmonary tuberculosis, while stability of mRNA encoding the antagonistic splice variant, IL-4δ2, is not

SummaryThe prototype Th2 cytokine IL-4, and its competitive antagonist IL-4δ2, may be important determinants of outcome in human tuberculosis (TB). However, there are no data on how gene expression of these cytokines is regulated.To evaluate this the stability of IL-4 and IL-4δ2 mRNA after the addition of actinomycin-D, was evaluated in whole blood from subjects with pulmonary TB and uninfected healthy volunteers.The Th2/Th1 (IL-4/IFN-γ) mRNA ratio in unstimulated cells in whole blood was significantly greater in TB subjects than in controls (p<0.05). The mRNA half-life of the agonist (IL-4), but not the antagonist (IL-4δ2), was significantly prolonged in subjects with TB compared to healthy volunteers (∼5-fold, p=0.0016), and the IL-4/IL-4δ2 ratio was higher in TB patients compared to controls (p<0.05).The differential stability of the Th2 agonist, IL-4, compared to the antagonist IL-4δ2, represents a hitherto undescribed post-transcriptional regulatory mechanism that may modulate the polarisation of Th1/Th2 responses in human TB.