Pleural effusion cytokine profiles in HIV/MTB co-infection

Pleural effusion is a common presentation in HIV/MTB co-infection. During infection, it is composed primarily of an extensive inflammatory cell infiltrate and an as yet poorly characterized cytokine milieu. Previous reports have shown significant expansion of CD4 T cells in pleural compartments of patients with active MTB infection. Both the immune infiltrate, and to a large degree, the pleural cytokine milieu, may augment viral dynamics and as a result, promote HIV replication in co-infected patients. This may have significant implications for clinical management of dually infected patients. To characterize the pleural effluent in HIV/MTB co-infected patients, we used cytokine array-based technology to profile key cytokines. Our data showed significantly elevated levels of IL6 and IFN-γ in pleural fluid from HIV/MTB co-infection compared to MTB alone (MTB/HIV vs MTB; IL6: 90.6pg/ml vs 85.6pg/ml; IFN-γ: 91.9pg/ml vs 85.4pg/ml). This observation may have reflected increases in systemic levels of these cytokines in dually infected patients (IL6: 32.1pg/ml vs 29.5pg/ml; IFN-γ: 7.6pg/ml vs 6.0pg/ml). We noted moderate inhibition of IL4 production in the MTB/HIV cohort (11.8pg/ml vs 13.8pg/ml). Interestingly, we report lower levels of TNF-α in the pleural compartment of co-infected patients (21.0pg/ml) relative to MTB infection alone (33.2pg/ml), despite stable systemic levels of the cytokine among all groups investigated. Taken together, our data suggests that co-infection with HIV may alter Th1/Th2 polarization dynamics at pleural sites. The high level of TNF-α at MTB pleural sites, in the absence of HIV, is suggestive of conventional pro-inflammatory, innate responses usually associated with tuberculosis.