Heightened systemic levels of anti-inflammatory cytokines in pulmonary tuberculosis and alterations following anti-tuberculosis treatment.

Pro-inflammatory cytokines are markers of disease severity and bacterial burden in pulmonary tuberculosis (PTB). However, the association of Type 2, regulatory and other anti-inflammatory cytokines with disease severity and bacterial burden in PTB is not well understood.To examine the association of anti-inflammatory cytokines with PTB, we examined the plasma levels of Type 2 (IL-4, IL-5, IL-13), regulatory (IL-10, TGFβ) and other anti-inflammatory (IL-19, IL-27, IL-37) cytokines in individuals with PTB, latent TB (LTB) or healthy controls (HC). We also examined the plasma levels of these cytokines in PTB individuals following anti-tuberculosis therapy (ATT).PTB individuals exhibited significantly higher plasma levels of IL-4, IL-13, IL-10, IL-19 and IL-27 in comparison to LTB and HC individuals and of TGFβ in comparison to HC individuals. In contrast, PTB individuals exhibited significantly lower plasma levels of IL-5 and IL-37 in comparison to both LTB and HC individuals. PTB individuals with bilateral or cavitary disease did not exhibit significantly different plasma levels of these cytokines in comparison to those with unilateral or non-cavitary disease nor did the cytokines exhibit any significant relationship with bacterial burdens. Finally, following ATT, the plasma levels of IL-4, IL-5 and IL-10 were significantly decreased, while the plasma levels of IL-13 and IL-37 were significantly increased in PTB individuals.Therefore, our data demonstrate that PTB is associated with altered levels of Type 2, regulatory and other anti-inflammatory cytokines, some of which are altered followed chemotherapy. Our data also reveal that anti-inflammatory cytokines are not markers of disease severity or bacterial burden in PTB. Elevations in anti-inflammatory cytokines might help prevent the detrimental effects of pro-inflammatory responses in PTB.