Background: Hyaluronan has been linked to asthma severity and inflammation. Results: We characterized the hyaluronan levels and its heavy chain modification in an experimental model of human asthma exacerbation. Conclusion: These data implicate hyaluronan and its heavy chain modification in human asthma severity. Significance: Repetitive asthma exacerbations exacerbate hyaluronan pathobiology, which contribute to the chronic inflammation associated with this disease.

Mycobacterium tuberculosis is the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control of M. tuberculosis requires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory(interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor ␤ [TGF-␤]) cytokines. IL-10 and TGF-␤ are produced by M. tuberculosis-infected macrophages. The effect of IL-10 and TGF-␤ on M. tuberculosis-reactive human CD4 ؉ and ␥␦ T cells, the two major human T-cell subsets activated by M. tuberculosis, was investigated. Both IL-10 and TGF-␤ inhibited proliferation and gamma interferon production by CD4 ؉ and ␥␦ T cells. IL-10 was a more potent inhibitor than TGF-␤ for both T-cell subsets. Combinations of IL-10 and TGF-␤ did not result in additive or synergistic inhibition. IL-10 inhibited ␥␦ and CD4 ؉ T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4 ؉ T cells and, to a lesser extent, for ␥␦ T cells. TGF-␤ inhibited both CD4 ؉ and ␥␦ T cells directly and had little effect on APC function for ␥␦ and CD4 ؉ T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression on M. tuberculosisinfected monocytes to a greater extent than TGF-␤. Neither cytokine affected the uptake of M. tuberculosis by monocytes. Thus, IL-10 and TGF-␤ both inhibited CD4 ؉ and ␥␦ T cells but differed in the mechanism used to inhibit T-cell responses to M. tuberculosis.

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