We examined the capacity of the naturally occurring inhibitors of transforming growth factor ␤ (TGF-␤), decorin and latency associated peptide (LAP), to reverse depressed T cell functions in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (TB) in vitro and to counteract the suppressive properties of TGF-␤ on mycobacterial replication in blood monocytes (MN) in vitro. T cell blastogenesis in response to purified protein derivative (PPD) in PBMCs of TB patients that were cocultured with decorin or LAP reached levels comparable to those observed in healthy tuberculin-responsive control subjects. Decorin and LAP were as effective as neutralizing antibody to TGF-␤ in correcting depressed T cell proliferation. Coculture of PBMCs from healthy PPD reactive individuals with neutralizing antibody to TGF-␤, decorin, or LAP did not affect T cell blastogenesis. Levels of interferon-␥ in cultures of PPDstimulated PBMCs from patients with TB increased by more than 2-fold in the presence of maximal concentrations of either of the inhibitors of TGF-␤, whereas TGF-␤ immunoreactivity declined to background levels. Coculture with optimal concentrations of decorin or LAP also led to reductions in mycobacterial growth in MN infected with Mycobacterium tuberculosis (MTB) in vitro by 51% and 62%, respectively, when compared with cells left untreated. In parallel, levels of immunoreactive TGF-␤ in MTB-infected MN cultures containing decorin or LAP decreased to background levels. These data indicate that the naturally occurring inhibitors of TGF-␤, decorin and LAP, efficiently abrogate the suppressive effects of TGF-␤ in PBMCs of TB patients and in MN infected with MTB in vitro. Therefore, these agents may be considered as adjuncts to antituberculous chemotherapy, and may be particularly useful in treatment of TB that is unresponsive to conventional chemotherapy.

Blood monocytes from patients with active pulmonary tuberculosis and age-matched healthy purified protein derivative-reactive donors were infected with human immunodeficiency virus type 1 (HIV-1)JR-FL in vitro to assess their susceptibility to productive infection by HIV-1. HIV-1 p24 levels (enzyme-linked immunosorbent assay) in supernatants of infected cells from patients with tuberculosis, albeit variable, were significantly higher at days 10-20 of culture; the maximum levels of p24 antigen were greater in supernatants of HIV-1-infected monocytes from patients than maximum levels for controls (p < 0.05). The maximum increment in p24 levels for patients also exceeded that for controls (p < 0.05). Entry of HIV-1 and/or initiation of reverse transcription, measured by polymerase chain reaction using HIV-1 R/U5 primer pairs, was variable and low in infected monocytes from both patients and controls, and did not correlate with HIV-1 p24 levels. The frequency of infected cells as assessed by endpoint dilution viral cultures was similar for both groups. Therefore, blood monocytes from patients with active tuberculosis can develop a highly productive infection with HIV-1 that does not appear to be due to enhanced HIV entry or higher frequency of infected cells. The enhanced susceptibility may result directly from activation of monocytes by exposure to Mycobacterium tuberculosis and its products in situ.

Clinicians should be aware of municipal tap water as a potential cause of methemoglobinemia and monitor for excessive levels of oxidants in dialysis water sources. The capacity of the hemodialysis equipment to clear chloramine can vary as a function of external factors. Using a reliable test method to identify chloramines in the water prior to entering the hemodialysis equipment is essential.